Symbol	Alias	Description	Function	Gene_Set	Species	Literature_Name	Literature_Link	KEGG_ID	KEGG_Name	Gene_ID
IL2RB	IL-2R Subunit Beta	Interleukin 2 Receptor Subunit Beta	Receptor for interleukin-2. This beta subunit is involved in receptor mediated endocytosis and transduces the mitogenic signals of IL2. Probably in association with IL15RA, involved in the stimulation of neutrophil phagocytosis by IL15.	others	Homo sapiens	Defective CD8 Signaling Pathways Delay Rejection in Older Recipients	10.1097/TP.0000000000000886	hsa04060	Cytokine-cytokine receptor interaction	3560
PSAT1	PSA	Phosphoserine Aminotransferase 1	Catalyzes the reversible conversion of 3-phosphohydroxypyruvate to phosphoserine and of 3-hydroxy-2-oxo-4-phosphonooxybutanoate to phosphohydroxythreonine.	others	Homo sapiens	Serine Metabolism Controls Dental Pulp Stem Cell Aging by Regulating the DNA Methylation of p16	10.1177/0022034520958374	hsa00260 hsa00260	Glycine, serine and threonine metabolism	29968
A2M	FWP007; S863-7; CPAMD5	alpha-2-macroglobulin	Alpha-2-macroglobulin is a serum pan-protease inhibitor that has been implicated in Alzheimer disease (AD) based on its ability to mediate the clearance and degradation of A beta, the major component of beta-amyloid deposits.	others	Homo sapiens	Alpha-2 Macroglobulin Is Genetically Associated With Alzheimer Disease	10.1038/1243	unknown	Unknown	2
AARS1	AlaRS	Alanyl-TRNA Synthetase 1	Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction: alanine is first activated by ATP to form Ala-AMP and then transferred to the acceptor end of tRNA(Ala) (PubMed:27622773, PubMed:27911835, PubMed:28493438). Also edits incorrectly charged tRNA(Ala) via its editing domain.	loss of proteostasis	Homo sapiens	Altered Sensory Neuron Development in CMT2D Mice Is Site-Specific and Linked to Increased GlyRS Levels	10.3389/fncel.2020.00232	hsa00970	Aminoacyl-tRNA biosynthesis	16
ABL1	JTK7; c-ABL	ABL proto-oncogene 1, non-receptor tyrosine kinase	c-Abl stimulates p73-mediated transactivation and apoptosis. This regulation of p73 by c-Abl in response to DNA damage is also demonstrated by a failure of ionizing-radiation-induced apoptosis after disruption of the c-Abl-p73 interaction.	genomic instability	Homo sapiens	p73 Is Regulated by Tyrosine Kinase c-Abl in the Apoptotic Response to DNA Damage	10.1038/21704	hsa04110	Cell cycle	25
ADCY1	ATP Pyrophosphate-Lyase 1	Adenylate cyclase type 1	Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. Mediates responses to increased cellular Ca2+/calmodulin levels. May be involved in regulatory processes in the central nervous system. May play a role in memory and learning. Plays a role in the regulation of the circadian rhythm of daytime contrast sensitivity probably by modulating the rhythmic synthesis of cyclic AMP in the retina.	altered intercellular communication	Homo sapiens	Expression and regulation of adenylyl cyclase isoforms in the human adrenal gland	10.1210/jcem.86.9.7837	hsa04211	Longevity regulating pathway	107
ADCY2	ATP Pyrophosphate-Lyase 2	Adenylate cyclase type 2	Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. Down-stream signaling cascades mediate changes in gene expression patterns and lead to increased IL6 production. Functions in signaling cascades downstream of the muscarinic acetylcholine receptors.	altered intercellular communication	Homo sapiens	Expression and regulation of adenylyl cyclase isoforms in the human adrenal gland	10.1210/jcem.86.9.7837	hsa04211	Longevity regulating pathway	108
ADCY3	ATP Pyrophosphate-Lyase 3	Adenylate cyclase type 3	Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. Participates in signaling cascades triggered by odorant receptors via its function in cAMP biosynthesis. Required for the perception of odorants. Required for normal sperm motility and normal male fertility. Plays a role in regulating insulin levels and body fat accumulation in response to a high fat diet.	altered intercellular communication	Homo sapiens	Expression and regulation of adenylyl cyclase isoforms in the human adrenal gland	10.1210/jcem.86.9.7837	hsa04211	Longevity regulating pathway	109
ADCY4	ATP Pyrophosphate-Lyase 4	Adenylate cyclase type 4	Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling.	altered intercellular communication	Homo sapiens	Characterization of the human adenylyl cyclase gene family: cDNA, gene structure, and tissue distribution of the nine isoforms	10.1081/rrs-120014589	hsa04211	Longevity regulating pathway	196883
ADCY5	ATP Pyrophosphate-Lyase 5	adenylate cyclase 5	Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. Mediates signaling downstream of ADRB1. Regulates the increase of free cytosolic Ca2+?in response to increased blood glucose levels and contributes to the regulation of Ca2+-dependent insulin secretion.	altered intercellular communication	Homo sapiens	Adenylyl Cyclase 5 Regulation by Gβγ Involves Isoform-Specific Use of Multiple Interaction Sites	10.1124/mol.115.099556	hsa04211	Longevity regulating pathway	111
ADCY6	ATP Pyrophosphate-Lyase 6	Adenylate cyclase type 6	Catalyzes the formation of the signaling molecule cAMP downstream of G protein-coupled receptors. Functions in signaling cascades downstream of beta-adrenergic receptors in the heart and in vascular smooth muscle cells. Functions in signaling cascades downstream of the vasopressin receptor in the kidney and has a role in renal water reabsorption. Functions in signaling cascades downstream of PTH1R and plays a role in regulating renal phosphate excretion. Functions in signaling cascades downstream of the VIP and SCT receptors in pancreas and contributes to the regulation of pancreatic amylase and fluid secretion. Signaling mediates cAMP-dependent activation of protein kinase PKA. This promotes increased phosphorylation of various proteins, including AKT. Plays a role in regulating cardiac sarcoplasmic reticulum Ca2+ uptake and storage, and is required for normal heart ventricular contractibility.	altered intercellular communication	Homo sapiens	Increased enzyme activity and beta-adrenergic mediated vasodilation in subjects expressing a single-nucleotide variant of human adenylyl cyclase 6	10.1161/ATVBAHA.107.145557	hsa04211	Longevity regulating pathway	112
ADCY7	ATP Pyrophosphate-Lyase 7	Adenylate cyclase type 7	Catalyzes the formation of cAMP in response to activation of G protein-coupled receptors. Functions in signaling cascades activated namely by thrombin and sphingosine 1-phosphate and mediates regulation of cAMP synthesis through synergistic action of the stimulatory G alpha protein with GNA13. Also, during inflammation, mediates zymosan-induced increase intracellular cAMP, leading to protein kinase A pathway activation in order to modulate innate immune responses through heterotrimeric G proteins G(12/13). Functions in signaling cascades activated namely by dopamine and C5 alpha chain and mediates regulation of cAMP synthesis through synergistic action of the stimulatory G protein with G beta:gamma complex.	altered intercellular communication	Homo sapiens	Regulation of cAMP responses by the G12/13 pathway converges on adenylyl cyclase VII	10.1074/jbc.M803281200	hsa04211	Longevity regulating pathway	113
ADCY8	ATP Pyrophosphate-Lyase 8	Adenylate cyclase type 8	Catalyzes the formation of cAMP in response to calcium entry leadings to cAMP signaling activation that affect processes suche as synaptic plasticity and insulin secretion. Plays a role in many brain functions, such as learning, memory, drug addiction, and anxiety modulation through regulation of synaptic plasticity by modulating long-term memory and long-term potentiation (LTP) through CREB transcription factor activity modulation. Plays a central role in insulin secretion by controlling glucose homeostasis through glucagon-like peptide 1 and glucose signaling pathway and maintains insulin secretion through calcium-dependent PKA activation leading to vesicle pool replenishment. Also, allows PTGER3 to induce potentiation of PTGER4-mediated PLA2 secretion by switching from a negative to a positive regulation, during the IL1B induced-dedifferentiation of smooth muscle cells.	altered intercellular communication	Homo sapiens	Molecular cloning of the human type VIII adenylyl cyclase	10.1016/0014-5793(94)00836-1	hsa04211	Longevity regulating pathway	114
ADCY9	ATP Pyrophosphate-Lyase 9	Adenylate cyclase type 9	Adenylyl cyclase that catalyzes the formation of the signaling molecule cAMP in response to activation of G protein-coupled receptors. Contributes to signaling cascades activated by CRH (corticotropin-releasing factor), corticosteroids and beta-adrenergic receptors.	altered intercellular communication	Homo sapiens	Cloning, chromosomal mapping, and regulatory properties of the human type 9 adenylyl cyclase (ADCY9)	10.1006/geno.1998.5293	hsa04211	Longevity regulating pathway	115
ADH1B	ADH2; HEL-S-117	alcohol dehydrogenase 1B (class I), beta polypeptide	Catalyzes the NAD-dependent oxidation of all-trans-retinol and its derivatives such as all-trans-4-hydroxyretinol and may participate in retinoid metabolism. In vitro can also catalyzes the NADH-dependent reduction of all-trans-retinal and its derivatives such as all-trans-4-oxoretinal.	genomic instability	Homo sapiens	Shortened telomeres in individuals with abuse in alcohol consumption	10.1002/ijc.25999	unknown	Unknown	125
ADH5	ADH-3; FALDH	alcohol dehydrogenase 5 (class III), chi polypeptide	Catalyzes the oxidation of long-chain primary alcohols and the oxidation of S-(hydroxymethyl) glutathione. Also oxidizes long chain omega-hydroxy fatty acids, such as 20-HETE, producing both the intermediate aldehyde, 20-oxoarachidonate and the end product, a dicarboxylic acid, (5Z,8Z,11Z,14Z)-eicosatetraenedioate.	others	Homo sapiens	Denitrosylate and live longer: how ADH5/GSNOR links mitophagy to aging	10.1080/15548627.2018.1475818	unknown	Unknown	128
ADIPOQ	ACRP30	Adiponectin receptor protein 1	Receptor for ADIPOQ, an essential hormone secreted by adipocytes that regulates glucose and lipid metabolism. Required for normal glucose and fat homeostasis and for maintaining a normal body weight. ADIPOQ-binding activates a signaling cascade that leads to increased AMPK activity, and ultimately to increased fatty acid oxidation, increased glucose uptake and decreased gluconeogenesis.	deregulated nutrient sensing	Homo sapiens	Cloning of adiponectin receptors that mediate antidiabetic metabolic effects	10.1038/nature01705	hsa04211	Longevity regulating pathway	9370
ADIPOR1	TESBP1A	Adiponectin receptor protein 1	Receptor for ADIPOQ, an essential hormone secreted by adipocytes that regulates glucose and lipid metabolism. Required for normal glucose and fat homeostasis and for maintaining a normal body weight. ADIPOQ-binding activates a signaling cascade that leads to increased AMPK activity, and ultimately to increased fatty acid oxidation, increased glucose uptake and decreased gluconeogenesis.	deregulated nutrient sensing	Homo sapiens	Cloning of adiponectin receptors that mediate antidiabetic metabolic effects	10.1038/nature01705	hsa04211	Longevity regulating pathway	51094
ADIPOR2	Progestin And AdipoQ Receptor Family Member 2	Adiponectin receptor protein 2	Receptor for ADIPOQ, an essential hormone secreted by adipocytes that regulates glucose and lipid metabolism. Required for normal body fat and glucose homeostasis. ADIPOQ-binding activates a signaling cascade that leads to increased PPARA activity, and ultimately to increased fatty acid oxidation and glucose uptake. Has intermediate affinity for globular and full-length adiponectin. Required for normal revascularization after chronic ischemia caused by severing of blood vessels.	deregulated nutrient sensing	Homo sapiens	Cloning of adiponectin receptors that mediate antidiabetic metabolic effects	10.1038/nature01705	hsa04211	Longevity regulating pathway	79602
AGPAT2	LPAAT-beta; BSCL	1-acylglycerol-3-phosphate O-acyltransferase 2	This gene encodes a member of the 1-acylglycerol-3-phosphate O-acyltransferase family. The protein is located within the endoplasmic reticulum membrane and converts lysophosphatidic acid to phosphatidic acid, the second step in de novo phospholipid biosynthesis. Mutations in this gene have been associated with congenital generalized lipodystrophy (CGL), or Berardinelli-Seip syndrome, a disease characterized by a near absence of adipose tissue and severe insulin resistance. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.	deregulated nutrient sensing	Homo sapiens	Human lipodystrophies: genetic and acquired diseases of adipose tissue	10.1159/000316893	unknown	Unknown	10555
AGTR1	Type-1 Angiotensin II Receptor	angiotensin II receptor, type 1	Receptor for angiotensin II. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.	altered intercellular communication	Homo sapiens	Cloning, expression, and characterization of a gene encoding the human angiotensin II type 1A receptor	10.1016/s0006-291x(05)80804-6	unknown	Unknown	185
AIFM1	AIF; CMTX4; PDCD8	apoptosis-inducing factor, mitochondrion-associated, 1	AIFM1 is an important player in apoptosis. Like cytochrome c, AIF is localized to mitochondria and released in response to death stimuli.	mitochondrial dysfunction	Homo sapiens	Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor	10.1126/science.1072221	hsa04210	Apoptosis	9131
AKT1	PKB; RAC	v-akt murine thymoma viral oncogene homolog 1	AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis.	cellular senescence	Homo sapiens	Akt negatively regulates the in vitro lifespan of human endothelial cells via a p53/p21-dependent pathway	10.1038/sj.emboj.7600045	hsa04211	Longevity regulating pathway	207
AKT1S1	Proline-Rich AKT1 Substrate 1	AKT1 substrate 1	Subunit of mTORC1, which regulates cell growth and survival in response to nutrient and hormonal signals. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-389', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. May also play a role in nerve growth factor-mediated neuroprotection.	deregulated nutrient sensing	Homo sapiens	Expression of proline-rich Akt-substrate PRAS40 in cell survival pathway and carcinogenesis	10.1111/j.1745-7254.2005.00184.x	hsa04211	Longevity regulating pathway	84335
AKT2	V-Akt Murine Thymoma Viral Oncogene Homolog 2	RAC-beta serine/threonine-protein kinase	AKT2 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation.	deregulated nutrient sensing	Homo sapiens	Molecular cloning of a second form of rac protein kinase	10.1091/mbc.2.12.1001	hsa04211	Longevity regulating pathway	208
AKT3	RAC-PK-Gamma	RAC-gamma serine/threonine-protein kinase	AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. AKT3 is the least studied AKT isoform. It plays an important role in brain development and is crucial for the viability of malignant glioma cells. AKT3 isoform may also be the key molecule in up-regulation and down-regulation of MMP13 via IL13. Required for the coordination of mitochondrial biogenesis with growth factor-induced increases in cellular energy demands. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis.	mitochondrial dysfunction	Homo sapiens	VEGF stimulation of mitochondrial biogenesis: requirement of AKT3 kinase	10.1096/fj.08-106468	hsa04211	Longevity regulating pathway	10000
ALDH2	ALDM; ALDHI	aldehyde dehydrogenase 2 family member	Reaction=an aldehyde + H2O + NAD(+) = a carboxylate + 2 H(+) + NADH.	others	Homo sapiens	Targeting Aldehyde Dehydrogenase 2: New Therapeutic Opportunities	10.1152/physrev.00017.2013	unknown	Unknown	217
ALDH9A1	ALDH4; ALDH7	aldehyde dehydrogenase 9 family member A1	Converts gamma-trimethylaminobutyraldehyde into gamma-butyrobetaine with high efficiency (in vitro). Can catalyze the irreversible oxidation of a broad range of aldehydes to the corresponding acids in an NAD-dependent reaction, but with low efficiency.	others	Homo sapiens	Impact of maternal aging on the molecular signature of human cumulus cells	10.1016/j.fertnstert.2012.08.012	unknown	Unknown	223
APEX1	REF1; HAP1; APX	APEX nuclease (multifunctional DNA repair enzyme) 1	APEX1 repairs oxidative DNA damage.	genomic instability	Homo sapiens	Alternative excision repair pathways	10.1101/cshperspect.a012617	unknown	Unknown	328
APOC3	Apolipoprotein C3; Apolipoprotein C-III	apolipoprotein C-III	Polymorphisms in the human APOC3 gene and promoter have been associated with lipoprotein profile, cardiovascular health, insulin (INS) sensitivity, and longevity.	deregulated nutrient sensing	Homo sapiens	Lipoprotein Genotype and Conserved Pathway for Exceptional Longevity in Humans	10.1371/journal.pbio.0040113	unknown	Unknown	345
APOE	AD2	apolipoprotein E	APOE activates a non-canonical MAP kinase cascade that enhances APP transcription and amyloid-β synthesis. Several polymorphisms in the APOE gene have been associated with Alzheimer’s disease.	others	Homo sapiens	ApoE2, ApoE3, and ApoE4 Differentially Stimulate APP Transcription and Aβ Secretion	10.1016/j.cell.2016.12.044	hsa05010	Alzheimer disease	348
APP	AD1	amyloid beta (A4) precursor protein	APP is an important player in Alzheimer's disease.	others	Homo sapiens	A Mutation in the Amyloid Precursor Protein Associated With Hereditary Alzheimer's Disease	10.1126/science.1925564	hsa05010	Alzheimer disease	351
APPL1	DIP13A	DCC-interacting protein 13-alpha	Multifunctional adapter protein that binds to various membrane receptors, nuclear factors and signaling proteins to regulate many processes, such as cell proliferation, immune response, endosomal trafficking and cell metabolism. Regulates signaling pathway leading to cell proliferation through interaction with RAB5A and subunits of the NuRD/MeCP1 complex. Functions as a positive regulator of innate immune response via activation of AKT1 signaling pathway by forming a complex with APPL1 and PIK3R1. Involved in trafficking of the TGFBR1 from the endosomes to the nucleus via microtubules in a TRAF6-dependent manner. Plays a role in cell metabolism by regulating adiponecting and insulin signaling pathways. Required for fibroblast migration through HGF cell signaling.	altered intercellular communication	Homo sapiens	Identification of a chromosome 3p14.3-21.1 gene, APPL, encoding an adaptor molecule that interacts with the oncoprotein-serine/threonine kinase AKT2	10.1038/sj.onc.1203080	hsa04211	Longevity regulating pathway	26060
APTX	FLJ20157; AOA; EAOH	aprataxin	The APTX protein is involved in DNA repair, and it interacts with DNA repair pathways as well as with ageing-related genes.	genomic instability	Homo sapiens	Aprataxin, the Causative Protein for EAOH Is a Nuclear Protein With a Potential Role as a DNA Repair Protein	10.1002/ana.10808	unknown	Unknown	54840
AR	AIS; NR3C4; SMAX1	androgen receptor	Androgen-AR plays key roles in the development of insulin and leptin resistance, which suggests that AR may contribute to certain age-related diseases such as type 2 diabetes and cardiovascular disease.	deregulated nutrient sensing	Homo sapiens	Tissue control of androgen action: The ups and downs of androgen receptor expression	10.1016/j.mce.2017.08.002	hsa04010	MAPK signaling pathway	367
AREG	AREGB; CRDGF	amphiregulin	Ligand of the EGF receptor/EGFR. Autocrine growth factor as well as a mitogen for a broad range of target cells including astrocytes, Schwann cells and fibroblasts.	senescence-associated secretory phenotype	Homo sapiens	The gene expression program of prostate fibroblast senescence modulates neoplastic epithelial cell proliferation through paracrine mechanisms	10.1158/0008-5472.CAN-05-1716	hsa04010	MAPK signaling pathway	374
ARHGAP1	Rho-Related Small GTPase Protein Activator	Rho GTPase activating protein 1	GTPase activator for the Rho, Rac and Cdc42 proteins, converting them to the putatively inactive GDP-bound state. Cdc42?seems to be the preferred substrate.	others	Homo sapiens	Characterization of rhoGAP. A GTPase-activating protein for rho-related small GTPases	PMID: 8288572	unknown	Unknown	392
ARID5A	MRF1	AT-Rich Interactive Domain-Containing Protein 5A	Members of the ARID protein family, including ARID5A, have diverse functions but all appear to play important roles in development, tissue-specific gene expression, and regulation of cell growth.	others	Homo sapiens	Differentially regulated gene expression in quiescence versus senescence and identification of ARID5A as a quiescence associated marker	10.1002/jcp.26227	unknown	Unknown	10865
ARNTL	Brain And Muscle ARNT-Like 1	aryl hydrocarbon receptor nuclear translocator-like	Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior.	others	Homo sapiens	Intermolecular Recognition Revealed by the Complex Structure of Human CLOCK-BMAL1 Basic Helix-Loop-Helix Domains With E-box DNA	10.1038/cr.2012.170	unknown	Unknown	406
ATF2	TREB7; CRE-BP1; HB16	activating transcription factor 2	TF2 is an important transcription factor involved in a variety of functions that may also be involved in oxidative stress response  and cellular growth arrest and senescence.	cellular senescence	Homo sapiens	Signal transduction in H2O2-induced senescence-like phenotype in human diploid fibroblasts	10.1016/s0891-5849(02)01044-4	hsa04211	Longevity regulating pathway	1386
ATF4	Tax-Responsive Enhancer Element-Binding Protein 67	Cyclic AMP-dependent transcription factor ATF-4	Transcription factor that binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3') and acts both as a regulator of normal metabolic and redox processes, and as a master transcription factor during the integrated stress response (ISR). Binds to asymmetric CRE's as a heterodimer and to palindromic CRE's as a homodimer. Core effector of the ISR, which is required for adaptation to various stress, such as endoplasmic reticulum (ER) stress, amino acid starvation, mitochondrial stress or oxidative stress. Protects cells against metabolic consequences of ER oxidation by promoting expression of genes linked to amino acid sufficiency and resistance to oxidative stress. Regulates the induction of DDIT3/CHOP and asparagine synthetase (ASNS) in response to amino acid deprivation or endoplasmic reticulum (ER) stress. Together with DDIT3/CHOP, mediates ER-mediated cell death by promoting expression of genes involved in cellular amino acid metabolic processes, mRNA translation and the unfolded protein response (UPR) in response to ER stress.	others	Homo sapiens	Isolation of cDNAs for DNA-binding proteins which specifically bind to a tax-responsive enhancer element in the long terminal repeat of human T-cell leukemia virus type I	PMCID: PMC239921	hsa04211	Longevity regulating pathway	468
ATF6B	Cyclic AMP-Dependent Transcription Factor ATF-6 Beta	Cyclic AMP-dependent transcription factor ATF-6 beta	Transcriptional factor that acts in the unfolded protein response (UPR) pathway by activating UPR target genes induced during ER stress. Binds DNA on the 5'-CCAC[GA]-3' half of the ER stress response element (ERSE) (5'-CCAATN9CCAC[GA]-3') when NF-Y is bound to ERSE.	loss of proteostasis	Homo sapiens	A novel Creb family gene telomeric of HLA-DRA in the HLA complex	10.1006/geno.1995.9891	hsa04211	Longevity regulating pathway	1388
ATG101	Chromosome 12 Open Reading Frame 44	Autophagy-related protein 101	Autophagy factor required for autophagosome formation. Stabilizes ATG13, protecting it from proteasomal degradation.	others	Homo sapiens	A novel, human Atg13 binding protein, Atg101, interacts with ULK1 and is essential for macroautophagy	10.4161/auto.5.5.8249	hsa04211	Longevity regulating pathway	60673
ATG13	KIAA0652	Autophagy-related protein 13	Autophagy factor required for autophagosome formation and mitophagy. Target of the TOR kinase signaling pathway that regulates autophagy through the control of the phosphorylation status of ATG13 and ULK1, and the regulation of the ATG13-ULK1-RB1CC1 complex. Through its regulation of ULK1 activity, plays a role in the regulation of the kinase activity of mTORC1 and cell proliferation.	others	Homo sapiens	A novel, human Atg13 binding protein, Atg101, interacts with ULK1 and is essential for macroautophagy	10.4161/auto.5.5.8249	hsa04211	Longevity regulating pathway	9776
ATG5	Apoptosis-Specific Protein	Autophagy protein 5	Involved in autophagic vesicle formation. Conjugation with ATG12, through a ubiquitin-like conjugating system involving ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes. Involved in mitochondrial quality control after oxidative damage, and in subsequent cellular longevity. Plays a critical role in multiple aspects of lymphocyte development and is essential for both B and T lymphocyte survival and proliferation. Required for optimal processing and presentation of antigens for MHC II. Involved in the maintenance of axon morphology and membrane structures, as well as in normal adipocyte differentiation. Promotes primary ciliogenesis through removal of OFD1 from centriolar satellites and degradation of IFT20 via the autophagic pathway.	others	Homo sapiens	Autophagy protein ATG5 interacts transiently with the hepatitis C virus RNA polymerase (NS5B) early during infection	10.1016/j.virol.2010.05.032	hsa04211	Longevity regulating pathway	9474
ATM	AT1; ATE	ATM serine/threonine kinase	Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor.	genomic instability	Homo sapiens	ATM Kinase Is Required for Telomere Elongation in Mouse and Human Cells	10.1016/j.celrep.2015.10.035	hsa04115	p53 signaling pathway	472
ATP5O	OSCP; ATPO	ATP synthase, H+ transporting, mitochondrial F1 complex, O subunit	ATP5O is a mitochondrial protein.	mitochondrial dysfunction	Homo sapiens	Identification of Mitochondrial Dysfunction in Hutchinson-Gilford Progeria Syndrome Through Use of Stable Isotope Labeling With Amino Acids in Cell Culture	10.1016/j.jprot.2013.08.008	unknown	Unknown	539
ATR	FRP1; SCKL; SCKL1	ATR serine/threonine kinase	ATR is involved in DNA repair by activating checkpoint signalling during genotoxic stresses including the phosphorylation of ageing-related proteins such as?BRCA1?and?TP53.	stem cell exhaustion	Homo sapiens	Deletion of the Developmentally Essential Gene ATR in Adult Mice Leads to Age-Related Phenotypes and Stem Cell Loss	10.1016/j.stem.2007.03.002	hsa04115	p53 signaling pathway	545
AXL	ARK; JTK11	AXL receptor tyrosine kinase	Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell survival, cell proliferation, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of AXL.	senescence-associated secretory phenotype	Homo sapiens	miR-34a Promotes Vascular Smooth Muscle Cell Calcification by Downregulating SIRT1 (Sirtuin 1) and Axl (AXL Receptor Tyrosine Kinase)	10.1161/ATVBAHA.118.311298	unknown	Unknown	558
BAK1	BAK; BAK-LIKE; BCL2L7	BCL2-antagonist/killer 1	Plays a role in the mitochondrial apoptosic process. Upon arrival of cell death signals, promotes mitochondrial outer membrane (MOM) permeabilization by oligomerizing to form pores within the MOM. This releases apoptogenic factors into the cytosol, including cytochrome c, promoting the activation of caspase 9 which in turn processes and activates the effector caspases.	mitochondrial dysfunction	Homo sapiens	A conserved domain in Bak, distinct from BH1 and BH2, mediates cell death and protein binding functions	https://doi.org/10.1002/j.1460-2075.1995.tb00246.x	hsa04210	Apoptosis	578
BAX	BCL2L4	BCL2-associated X protein	BAX is an important player in apoptosis.	others	Homo sapiens	Mitochondrial inner membrane permeabilisation enables mtDNA release during apoptosis	10.15252/embj.201899238	hsa04211	Longevity regulating pathway	581
BCL10	CARMEN; CIPER; CLAP	BCL10 immune signaling adaptor	Involved in adaptive immune response (PubMed:25365219). Promotes apoptosis, pro-caspase-9 maturation and activation of NF-kappa-B via NIK and IKK. May be an adapter protein between upstream TNFR1-TRADD-RIP complex and the downstream NIK-IKK-IKAP complex.	NF-κB related gene	Homo sapiens	Antagonistic crosstalk between NF-κB and SIRT1 in the regulation of inflammation and metabolic disorders	10.1016/j.cellsig.2013.06.007	hsa04064	NF-kappa B signaling pathway	8915
BCL2	Bcl-2	B-cell CLL/lymphoma 2	Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability.	others	Homo sapiens	Regulation of apoptosis resistance and ontogeny of age-dependent diseases	10.1016/s0531-5565(96)00156-8	hsa04115	p53 signaling pathway	596
BCL2A1	BFL1; GRS	BCL2 related protein A1	Retards apoptosis induced by IL-3 deprivation. May function in the response of hemopoietic cells to external signals and in maintaining endothelial survival during infection.	NF-κB related gene	Homo sapiens	Inhibition of mitochondrial cytochrome c release and suppression of caspases by gamma-tocotrienol prevent apoptosis and delay aging in stress-induced premature senescence of skin fibroblasts	10.1155/2012/785743	hsa04064	NF-kappa B signaling pathway	597
BCL2L1	Bcl-XL; Bcl-XS	BCL2 like 1	Potent inhibitor of cell death. Inhibits activation of caspases. Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane.	NF-κB related gene	Homo sapiens	Human exceptional longevity: transcriptome from centenarians is distinct from septuagenarians and reveals a role of Bcl-xL in successful aging	10.18632/aging.101078	hsa04064	NF-kappa B signaling pathway	598
BDNF	ANON2; BULN2	brain-derived neurotrophic factor	BDNF is a growth factor that promotes neuronal survival and is involved in numerous neuronal responses.	cellular senescence	Homo sapiens	The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function	10.1016/s0092-8674(03)00035-7	hsa04010	MAPK signaling pathway	627
BIRC2	CIAP1; API1	baculoviral IAP repeat containing 2	Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, mitogenic kinase signaling, and cell proliferation, as well as cell invasion and metastasis.	NF-κB related gene	Homo sapiens	A serum protein signature of APOE genotypes in centenarians	10.1111/acel.13023	hsa04064	NF-kappa B signaling pathway	329
BIRC3	C-IAP2; RNF49	Baculoviral IAP Repeat Containing 3	Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, mitogenic kinase signaling and cell proliferation, as well as cell invasion and metastasis.	NF-κB related gene	Homo sapiens	Differential regulation of inhibitors of apoptosis proteins in Alzheimer's disease brains	10.1016/j.nbd.2006.12.017	hsa04064	NF-kappa B signaling pathway	330
BLM	RECQL3	Bloom syndrome, RecQ helicase-like	ATP-dependent DNA helicase that unwinds single- and double-stranded DNA in a 3'-5' direction.	genomic instability	Homo sapiens	Bloom's Syndrome: Why Not Premature Aging?: A Comparison of the BLM and WRN Helicases	10.1016/j.arr.2016.05.010	unknown	Unknown	641
BMI1	RNF51; PCGF4	BMI1 proto-oncogene, polycomb ring finger	BMI1 is an oncogene involved in transcriptional regulation by remodelling chromatin. It may also be involved in development.	stem cell exhaustion	Homo sapiens	Bmi1 is down-regulated in the aging brain and displays antioxidant and protective activities in neurons	10.1371/journal.pone.0031870	hsa04550	Signaling pathways regulating pluripotency of stem cells	648
BMP2	BDA2; BMP2	Bone Morphogenetic Protein 2	Induces cartilage and bone formation. Stimulates the differentiation of myoblasts into osteoblasts via the EIF2AK3-EIF2A- ATF4 pathway. BMP2 activation of EIF2AK3 stimulates phosphorylation of EIF2A which leads to increased expression of ATF4 which plays a central role in osteoblast differentiation.	senescence-associated secretory phenotype	Homo sapiens	Long noncoding RNA Bmncr regulates mesenchymal stem cell fate during skeletal aging	10.1172/JCI99044	hsa04350	TGF-beta signaling pathway	650
BMP6	VGR1; VGR	Bone Morphogenetic Protein 6	Induces cartilage and bone formation.	senescence-associated secretory phenotype	Homo sapiens	Increased BMP6 Levels in the Brains of Alzheimer's Disease Patients and APP Transgenic Mice Are Accompanied by Impaired Neurogenesis	10.1523/JNEUROSCI.1305-10.2010	hsa04350	TGF-beta signaling pathway	654
BRCA1	RNF53; BROVCA1	breast cancer 1, early onset	E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.	genomic instability	Homo sapiens	Large-scale Genomic Analyses Link Reproductive Aging to Hypothalamic Signaling, Breast Cancer Susceptibility and BRCA1-mediated DNA Repair	10.1038/ng.3412	hsa04151	PI3K-Akt signaling pathway	672
BRCA2	FAD1; BRCC2; XRCC11	breast cancer 2, early onset	XRCC1 is a molecular scaffold protein that assembles multi-protein complexes involved in DNA single-strand break repair.Cells from Homo sapiens patients with mutations in BRCA2 exhibited reduced rates of DNA repair and elevated levels of protein ADP-ribosylation.	genomic instability	Homo sapiens	XRCC1 Mutation Is Associated With PARP1 Hyperactivation and Cerebellar Ataxia	10.1038/nature20790	unknown	Unknown	675
BSCL2	GNG3LG; SPG17	Berardinelli-Seip congenital lipodystrophy 2 (seipin)	It is a regulator of lipid catabolism essential for adipocyte differentiation. May also be involved in the central regulation of energy homeostasis. Necessary for correct lipid storage and lipid droplets maintenance; may play a tissue-autonomous role in controlling lipid storage in adipocytes and in preventing ectopic lipid droplet formation in non-adipose tissues.	deregulated nutrient sensing	Homo sapiens	Genetic Syndromes in Man With Potential Relevance to the Pathobiology of Aging	PMID:?147113	unknown	Unknown	26580
BTK	AGMX1; BPK	Bruton Tyrosine Kinase	Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. After BCR engagement and activation at the plasma membrane, phosphorylates PLCG2 at several sites, igniting the downstream signaling pathway through calcium mobilization, followed by activation of the protein kinase C (PKC) family members.	NF-κB related gene	Homo sapiens	BTK Modulates p53 Activity to Enhance Apoptotic and Senescent Responses	10.1158/0008-5472.CAN-16-0690	hsa04064	NF-kappa B signaling pathway	695
BUB1B	BUBR1; MAD3L; Bub1A	BUB1 mitotic checkpoint serine/threonine kinase B	BUB1B is a mitotic checkpoint that controls chromosome segregation and maintains genetic stability. Inhibit aging.	genomic instability	Homo sapiens	Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B	10.1038/ng1449	hsa04110	Cell cycle	701
BUB3	Mitotic Checkpoint Protein BUB3	BUB3 mitotic checkpoint protein	It has a dual function in spindle-assembly checkpoint signaling and in promoting the establishment of correct kinetochore-microtubule (K-MT) attachments. Promotes the formation of stable end-on bipolar attachments. Necessary for kinetochore localization of BUB1. Regulates chromosome segregation during oocyte meiosis. The BUB1/BUB3 complex plays a role in the inhibition of anaphase-promoting complex or cyclosome (APC/C) when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. This complex can also phosphorylate MAD1L1.	others	Homo sapiens	The human homologue of Bub3 is required for kinetochore localization of Bub1 and a Mad3/Bub1-related protein kinase	10.1083/jcb.142.1.1	hsa04110	Cell cycle	9184
C1QA	Complement C1q Chain A	complement component 1, q subcomponent, A chain	C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes.	others	Homo sapiens	Homozygous single nucleotide polymorphism of the complement C1QA gene is associated with decreased levels of C1q in patients with subacute cutaneous lupus erythematosus	10.1191/0961203303lu329oa	unknown	Unknown	712
CACNA1A	Cav2.1; EA2; APCA	calcium channel, voltage-dependent, P/Q type, alpha 1A subunit	CACNA1A mediates calcium ions in a variety of processes such as cell division and gene expression.	others	Homo sapiens	Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4	10.1016/s0092-8674(00)81373-2	hsa04010	MAPK signaling pathway	773
CALR	Sicca Syndrome Antigen A;CRP55	Calreticulin	Calcium-binding chaperone that promotes folding, oligomeric assembly and quality control in the endoplasmic reticulum (ER) via the calreticulin/calnexin cycle. This lectin interacts transiently with almost all of the monoglucosylated glycoproteins that are synthesized in the ER. Interacts with the DNA-binding domain of NR3C1 and mediates its nuclear export. Involved in maternal gene expression regulation. May participate in oocyte maturation via the regulation of calcium homeostasis (By similarity).	loss of proteostasis	Homo sapiens	Calreticulin functions as a molecular chaperone in the biosynthesis of myeloperoxidase.	10.1074/jbc.270.9.4741	hsa04141	Protein processing in endoplasmic reticulum	811
CAMK4	CAM Kinase- GR	calcium/calmodulin-dependent protein kinase type IV	Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK4 signaling cascade and regulates, mainly by phosphorylation, the activity of several transcription activators, such as CREB1, MEF2D, JUN and RORA, which play pivotal roles in immune response, inflammation, and memory consolidation. In the thymus, regulates the CD4+/CD8+ double positive thymocytes selection threshold during T-cell ontogeny. In CD4 memory T-cells, is required to link T-cell antigen receptor (TCR) signaling to the production of IL2, IFNG and IL4 (through the regulation of CREB and MEF2). Regulates the differentiation and survival phases of osteoclasts and dendritic cells (DCs). Mediates DCs survival by linking TLR4 and the regulation of temporal expression of BCL2.	others	Homo sapiens	Activation mechanisms for Ca2+/calmodulin-dependent protein kinase IV. Identification of a brain CaM-kinase IV kinase	PMID: 7961813	hsa04211	Longevity regulating pathway	814
CAMKK2	CaM-Kinase Kinase Beta	Calcium/calmodulin-dependent protein kinase kinase 2	Calcium/calmodulin-dependent protein kinase belonging to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Isoform 1, isoform 2 and isoform 3 phosphorylate CAMK1 and CAMK4. Isoform 3 phosphorylates CAMK1D. Isoform 4, isoform 5 and isoform 6 lacking part of the calmodulin-binding domain are inactive. Efficiently phosphorylates 5'-AMP-activated protein kinase (AMPK) trimer, including that consisting of PRKAA1, PRKAB1 and PRKAG1. This phosphorylation is stimulated in response to Ca2+ signals. Seems to be involved in hippocampal activation of CREB1. May play a role in neurite growth. Isoform 3 may promote neurite elongation, while isoform 1 may promoter neurite branching.	others	Homo sapiens	Human Ca2+/calmodulin-dependent protein kinase kinase beta gene encodes multiple isoforms that display distinct kinase activity	10.1074/jbc.M011720200	hsa04211	Longevity regulating pathway	10645
CARD10	BIMP1	Caspase Recruitment Domain Family Member 10	Activates NF-kappa-B via BCL10 and IKK.	NF-κB related gene	Homo sapiens	Whole-exome sequencing and imaging genetics identify functional variants for rate of change in hippocampal volume in mild cognitive impairment	10.1038/mp.2013.24	hsa04064	NF-kappa B signaling pathway	29775
CAT	Catalase; EC 1.11.1.6; Epididymis Secretory Sperm Binding Protein	catalase	Cardiac-specific overexpression prolongs lifespan in mice. Catalase protects cardiomyocytes from ageing-induced contractile defects and protein damage.	others	Homo sapiens	Role of Catalase in Oxidative Stress- and Age-Associated Degenerative Diseases	10.1155/2019/9613090	hsa04211	Longevity regulating pathway	847
CBX7	Chromobox Homolog 7	chromobox protein homolog 7	Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. Promotes histone H3 trimethylation at 'Lys-9' (H3K9me3). Binds to trimethylated lysine residues in histones, and possibly also other proteins. Regulator of cellular lifespan by maintaining the repression of CDKN2A, but not by inducing telomerase activity.	genomic instability	Homo sapiens	Several distinct polycomb complexes regulate and co-localize on the INK4a tumor suppressor locus	10.1371/journal.pone.0006380	unknown	Unknown	23492
CCL1	SISe; TCA3	C-C Motif Chemokine Ligand 1	Cytokine that is chemotactic for monocytes but not for neutrophils. Binds to CCR8.	senescence-associated secretory phenotype	Homo sapiens	Normal ageing is associated with an increase in Th2 cells, MCP-1 (CCL1) and RANTES (CCL5), with differences in sCD40L and PDGF-AA between sexes	10.1111/j.1365-2249.2012.04644.x	unknown	Unknown	6346
CCL13	SCYL1; NCC1	C-C Motif Chemokine Ligand 13	Chemotactic factor that attracts monocytes, lymphocytes, basophils and eosinophils, but not neutrophils. Signals through CCR2B and CCR3 receptors. Plays a role in the accumulation of leukocytes at both sides of allergic and non-allergic inflammation.	senescence-associated secretory phenotype	Homo sapiens	Increased cardiovascular and atherosclerosis markers in blood of older patients with atopic dermatitis	10.1016/j.anai.2019.10.013	hsa04064	NF-kappa B signaling pathway	6357
CCL19	SCYA19; CKb11	C-C Motif Chemokine Ligand 19	May play a role not only in inflammatory and immunological responses but also in normal lymphocyte recirculation and homing. May play an important role in trafficking of T-cells in thymus, and T-cell and B-cell migration to secondary lymphoid organs. Binds to chemokine receptor CCR7. Recombinant CCL19 shows potent chemotactic activity for T-cells and B-cells but not for granulocytes and monocytes. Binds to atypical chemokine receptor ACKR4 and mediates the recruitment of beta-arrestin (ARRB1/2) to ACKR4.	NF-κB related gene	Homo sapiens	Mechanisms of aging in senescence-accelerated mice	10.1186/gb-2005-6-6-r48	hsa04064	NF-kappa B signaling pathway	6363
CCL20	MIP3A; CKb4	C-C Motif Chemokine Ligand 20	Acts as a ligand for C-C chemokine receptor CCR6. Signals through binding and activation of CCR6 and induces a strong chemotactic response and mobilization of intracellular calcium ions.	senescence-associated secretory phenotype	Homo sapiens	SIRT1/FoxO3 axis alteration leads to aberrant immune responses in bronchial epithelial cells	10.1111/jcmm.13509	unknown	Unknown	6364
CCL21	CKb9; TCA4	C-C Motif Chemokine Ligand 21	Inhibits hemopoiesis and stimulates chemotaxis. Chemotactic in vitro for thymocytes and activated T-cells, but not for B-cells, macrophages, or neutrophils. Shows preferential activity towards naive T-cells.	NF-κB related gene	Homo sapiens	Distinctive immunoregulatory effects of adenosine on T cells of older humans	10.1096/fj.11-197046	hsa04064	NF-kappa B signaling pathway	6366
CCL26	SCYA26; IMAC	C-C Motif Chemokine Ligand 26	Chemoattractant for eosinophils and basophils.	senescence-associated secretory phenotype	Homo sapiens	Age-specific changes in the molecular phenotype of patients with moderate-to-severe atopic dermatitis	10.1016/j.jaci.2019.01.015	unknown	Unknown	10344
CCL3	MIP1A; SCYA3	C-C Motif Chemokine Ligand 3	Monokine with inflammatory and chemokinetic properties. Binds to CCR1, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells.	senescence-associated secretory phenotype	Homo sapiens	Age-related pro-inflammatory and pro-angiogenic changes in human aqueous humor	10.18240/ijo.2018.02.03	unknown	Unknown	6348
CCL4	MIP1B; SCYA4	C-C Motif Chemokine Ligand 4	Monokine with inflammatory and chemokinetic properties. Binds to CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant MIP-1-beta induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). The processed form MIP-1-beta(3-69) retains the abilities to induce down-modulation of surface expression of the chemokine receptor CCR5 and to inhibit the CCR5-mediated entry of HIV-1 in T-cells.	NF-κB related gene	Homo sapiens	MicroRNA-125b modulates inflammatory chemokine CCL4 expression in immune cells and its reduction causes CCL4 increase with age	10.1111/acel.12294	hsa04064	NF-kappa B signaling pathway	6351
CCL7	SCYA6; SCYA7	C-C Motif Chemokine Ligand 7	Chemotactic factor that attracts monocytes and eosinophils, but not neutrophils. Augments monocyte anti-tumor activity.	senescence-associated secretory phenotype	Homo sapiens	Increased cardiovascular and atherosclerosis markers in blood of older patients with atopic dermatitis	10.1016/j.anai.2019.10.013	unknown	Unknown	6354
CCNA2	CCNA; CCN1	cyclin A2	Involved in cell cycle control， binds and activates CDK2 and promotes transition through G1/S and G2/M.	stem cell exhaustion	Homo sapiens	Structure and cell cycle-regulated transcription of the human cyclin A gene	10.1073/pnas.91.12.5490	hsa04218	Cellular senescence	890
CD14	CD14 Antigen	CD14 Molecule	Coreceptor for bacterial lipopolysaccharide (PubMed:1698311, PubMed:23264655). In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating the innate immune response to bacterial lipopolysaccharide (LPS).	NF-κB related gene	Homo sapiens	Association of CD14 with incident dementia and markers of brain aging and injury	10.1212/WNL.0000000000008682	hsa04064	NF-kappa B signaling pathway	929
CD40LG	CD154; Gp39	CD40 Ligand	Cytokine that acts as a ligand to CD40/TNFRSF5. Costimulates T-cell proliferation and cytokine production.	NF-κB related gene	Homo sapiens	Elderly dendritic cells respond to LPS/IFN-γ and CD40L stimulation despite incomplete maturation	10.1371/journal.pone.0195313	hsa04064	NF-kappa B signaling pathway	959
CD55	DAF; TC	CD55 Molecule (Cromer Blood Group)	This protein recognizes C4b and C3b fragments that condense with cell-surface hydroxyl or amino groups when nascent C4b and C3b are locally generated during C4 and c3 activation.	senescence-associated secretory phenotype	Homo sapiens	Early and extensive CD55 loss from red blood cells supports a causal role in malarial anaemia	10.1186/1475-2875-10-386	unknown	Unknown	1604
CD9	MIC3; P24	CD9 Molecule	Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion.	senescence-associated secretory phenotype	Homo sapiens	CD9 expression in vascular aging and atherosclerosis	10.14670/HH-18-268	unknown	Unknown	928
CDC42	Cell Division Control Protein 42 Homolog	cell division cycle 42	Probably involved in the organization of the actin cytoskeleton by acting downstream of CDC42, inducing actin filament assembly. Alters CDC42-induced cell shape changes. In activated T-cells, may play a role in CDC42-mediated F-actin accumulation at the immunological synapse. May play a role in early contractile events in phagocytosis in macrophages.	others	Homo sapiens	Cdc42: An Essential Rho-Type GTPase Controlling Eukaryotic Cell Polarity	10.1128/MMBR.63.1.54-105.1999	hsa04010	MAPK signaling pathway	998
CDK1	CDC28A; CDC2	cyclin-dependent kinase 1	An important regulator of the cell cycle, CDK1 also appears to be involved in apoptosis.	cellular senescence	Homo sapiens	TIAR marks nuclear G2/M transition granules and restricts CDK1 activity under replication stress	10.15252/embr.201846224	hsa04115	p53 signaling pathway	983
CDK7	CDK-Activating Kinase 1	cyclin-dependent kinase 7	Serine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription. Cyclin-dependent kinases (CDKs) are activated by the binding to a cyclin and mediate the progression through the cell cycle. Each different complex controls a specific transition between 2 subsequent phases in the cell cycle. Required for both activation and complex formation of CDK1/cyclin-B during G2-M transition, and for activation of CDK2/cyclins during G1-S transition (but not complex formation). Its expression and activity are constant throughout the cell cycle. Upon DNA damage, triggers p53/TP53 activation by phosphorylation, but is inactivated in turn by p53/TP53; this feedback loop may lead to an arrest of the cell cycle and of the transcription, helping in cell recovery, or to apoptosis. Required for DNA-bound peptides-mediated transcription and cellular growth inhibition.	others	Homo sapiens	novel cyclin associates with MO15/CDK7 to form the CDK-activating kinase	10.1016/0092-8674(94)90535-5	hsa04110	Cell cycle	1022
CDKN1A	CAP20	cyclin-dependent kinase inhibitor 1A (p21, Cip1)	May be involved in p53/TP53 mediated inhibition of cellular proliferation in response to DNA damage. Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localization and assembly of cyclin D-CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex. Inhibits DNA synthesis by DNA polymerase delta by competing with POLD3 for PCNA binding. Plays an important role in controlling cell cycle progression and DNA damage-induced G2 arrest.	genomic instability	Homo sapiens	The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases	10.1016/0092-8674(93)90499-g	hsa04115	p53 signaling pathway	1026
CDKN2A	CDK4I; p16; INK4a	cyclin-dependent kinase inhibitor 2A	The CDKN2A gene encodes different transcripts involved mostly in cell cycle regulation and cellular senescence, including the tumour suppressor proteins p16 and p19.	cellular senescence	Homo sapiens	Involvement of the INK4a/Arf Gene Locus in Senescence	10.1046/j.1474-9728.2003.00048.x	hsa04115	p53 signaling pathway	1029
CDKN2B	P14-INK4b	cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)	Interacts strongly with CDK4 and CDK6. Potent inhibitor. Potential effector of TGF-beta induced cell cycle arrest.	others	Homo sapiens	MTAP and CDKN2B genes are associated with myocardial infarction in Chinese Hans	10.1016/j.clinbiochem.2009.02.021	hsa04218	Cellular senescence	1030
CEBPA	C/EBP-alpha; CEBP	CCAAT/enhancer binding protein (C/EBP), alpha	CEBPA is a transcription factor expressed in adipose tissues that modulates the expression of leptin (LEP). CEBPA-null die shortly after birth.	others	Homo sapiens	Aging and liver regeneration	10.1016/j.tem.2009.01.005	unknown	Unknown	1050
CEBPB	LAP; CRP2; NFIL6	CCAAT/enhancer binding protein (C/EBP), beta	Like CEBPA, CEBPB is a transcription factor involved in fat metabolism. CEBPB also appears to play a role in liver regeneration.	others	Homo sapiens	Epigenome-wide association studies identify DNA methylation associated with kidney function	10.1038/s41467-017-01297-7	hsa04657	IL-17 signaling pathway	1051
CETP	BPI Fold Containing Family F	cholesteryl ester transfer protein, plasma	Involved in the transfer of neutral lipids, including cholesteryl ester and triglyceride, among lipoprotein particles. Allows the net movement of cholesteryl ester from high density lipoproteins/HDL to triglyceride-rich very low density lipoproteins/VLDL, and the equimolar transport of triglyceride from VLDL to HDL. Regulates the reverse cholesterol transport, by which excess cholesterol is removed from peripheral tissues and returned to the liver for elimination.	deregulated nutrient sensing	Homo sapiens	Cloning and Sequencing of Human Cholesteryl Ester Transfer Protein Cdna	10.1038/327632a0	unknown	Unknown	1071
CFLAR	FLAME; CFLIP	CASP8 And FADD Like Apoptosis Regulator	Apoptosis regulator protein which may function as a crucial link between cell survival and cell death pathways in mammalian cells. Acts as an inhibitor of TNFRSF6 mediated apoptosis.	NF-κB related gene	Homo sapiens	The apoptotic transcriptome of the human MII oocyte: characterization and age-related changes	10.1007/s10495-012-0783-5	hsa04064	NF-kappa B signaling pathway	8837
CHCHD2	C7orf17; MIX17B; MNRR1	coiled-coil-helix-coiled-coil-helix domain containing 2	Mutations in the CHCHD2 gene have been linked to autosomal dominant forms of Parkinson's disease (PD).	others	Homo sapiens	CHCHD2 mutational screening in Brazilian patients with familial Parkinson's disease	10.1016/j.neurobiolaging.2018.09.026	unknown	Unknown	51142
CHEK2	Serine/Threonine-Protein Kinase Chk2	checkpoint kinase 2	Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest. Regulates DNA repair through phosphorylation of BRCA2, enhancing the association of RAD51 with chromatin which promotes DNA repair by homologous recombination. Also stimulates the transcription of genes involved in DNA repair (including BRCA2) through the phosphorylation and activation of the transcription factor FOXM1. Regulates apoptosis through the phosphorylation of p53/TP53, MDM4 and PML. Also controls the transcription of pro-apoptotic genes through phosphorylation of the transcription factor E2F1.	genomic instability	Homo sapiens	Chk2 and REGγ-dependent DBC1 Regulation in DNA Damage Induced Apoptosis	10.1093/nar/gku1065	hsa04115	p53 signaling pathway	11200
CISD2	CDGSH Iron Sulfur Domain 2	CDGSH iron sulfur domain 2	Regulator of autophagy that contributes to antagonize BECN1-mediated cellular autophagy at the endoplasmic reticulum. Participates in the interaction of BCL2 with BECN1 and is required for BCL2-mediated depression of endoplasmic reticulum Ca2+?stores during autophagy. Contributes to BIK-initiated autophagy, while it is not involved in BIK-dependent activation of caspases. Involved in life span control, probably via its function as regulator of autophagy.	others	Homo sapiens	A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2	10.1086/520961	unknown	Unknown	493856
CLOCK	Circadian Locomoter Output Cycles Protein Kaput	clock circadian regulator	Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 25 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior.	others	Homo sapiens	Intermolecular Recognition Revealed by the Complex Structure of Human CLOCK-BMAL2 Basic Helix-Loop-Helix Domains With E-box DNA	10.1038/cr.2012.171	unknown	Unknown	9575
CLU	SGP-2; SP-40; TRPM-2	clusterin	It may be involved in apoptosis.	cellular senescence	Homo sapiens	Serum Levels of the Senescence Biomarker clusterin/apolipoprotein J Increase Significantly in Diabetes Type II and During Development of Coronary Heart Disease or at Myocardial Infarction	10.1016/s0531-5565(02)00139-0	unknown	Unknown	1191
CNR1	CANN6	cannabinoid receptor 1 (brain)	G-protein coupled receptor for endogenous cannabinoids (eCBs), including N-arachidonoylethanolamide (also called anandamide or AEA) and 2-arachidonoylglycerol (2-AG), as well as phytocannabinoids, such as delta9-tetrahydrocannabinol (THC). Mediates many cannabinoid-induced effects, acting, among others, on food intake, memory loss, gastrointestinal motility, catalepsy, ambulatory activity, anxiety, chronic pain. Signaling typically involves reduction in cyclic AMP. In the hypothalamus, may have a dual effect on mitochondrial respiration depending upon the agonist dose and possibly upon the cell type. May also affect de novo cholesterol synthesis and HDL-cholesteryl ether uptake. Peripherally modulates energy metabolism.	deregulated nutrient sensing	Homo sapiens	CB1 cannabinoid receptor activity is modulated by the cannabinoid receptor interacting protein CRIP 1a	10.1124/mol.107.039263	unknown	Unknown	1268
COQ7	CLK-1; CAT5	coenzyme Q7 homolog, ubiquinone (yeast)	2-fold reduction of MCLK1 expression in mice affects mitochondrial function substantially, and also exhibit surprisingly high levels of oxidative damage and early mitochondrial dysfunction.	mitochondrial dysfunction	Homo sapiens	Conservation of the Caenorhabditis elegans timing gene clk-1 from yeast to human: a gene required for ubiquinone biosynthesis with potential implications for aging	10.1007/s003359901147	unknown	Unknown	10229
CREB1	Cyclic Adenosine 3',5'-Monophosphate Response Element Binding Protein	cAMP responsive element binding protein 1	This gene encodes a transcription factor that is a member of the leucine zipper family of DNA binding proteins. This protein binds as a homodimer to the cAMP-responsive element, an octameric palindrome.	genomic instability	Homo sapiens	Direct regulation of CREB transcriptional activity by ATM in response to genotoxic stress	10.1073/pnas.0307718101	hsa04211	Longevity regulating pathway	1385
CREB3	Transcription Factor LZIP-Alpha	cyclic AMP-responsive element-binding protein 3	Endoplasmic reticulum (ER)-bound sequence-specific transcription factor that directly binds DNA and activates transcription. Plays a role in the unfolded protein response (UPR), promoting cell survival versus ER stress-induced apoptotic cell death. Also involved in cell proliferation, migration and differentiation, tumor suppression and inflammatory gene expression. Acts as a positive regulator of LKN-1/CCL15-induced chemotaxis signaling of leukocyte cell migration. Associates with chromatin to the HERPUD1 promoter. Also induces transcriptional activation of chemokine receptors.	loss of proteostasis	Homo sapiens	Luman is capable of binding and activating transcription from the unfolded protein response element	10.1016/j.bbrc.2005.03.141	hsa04211	Longevity regulating pathway	10488
CREB3L1	OASIS	cyclic AMP-responsive element-binding protein 3-like protein 1	Transcription factor involved in unfolded protein response (UPR). Binds the DNA consensus sequence 5'-GTGXGCXGC-3'. In the absence of endoplasmic reticulum (ER) stress, inserted into ER membranes, with N-terminal DNA-binding and transcription activation domains oriented toward the cytosolic face of the membrane. In response to ER stress, transported to the Golgi, where it is cleaved in a site-specific manner by resident proteases S1P/MBTPS1 and S2P/MBTPS2. The released N-terminal cytosolic domain is translocated to the nucleus to effect transcription of specific target genes. Plays a critical role in bone formation through the transcription of COL1A1, and possibly COL1A2, and the secretion of bone matrix proteins. Directly binds to the UPR element (UPRE)-like sequence in an osteoblast-specific COL1A1 promoter region and induces its transcription. Does not regulate COL1A1 in other tissues, such as skin.	loss of proteostasis	Homo sapiens	OASIS is a transcriptional activator of CREB/ATF family with a transmembrane domain	10.1016/S0006-291X(02)00253-X	hsa04211	Longevity regulating pathway	90993
CREB3L2	B-ZIB Transcription Factor	cyclic AMP-responsive element-binding protein 3-like protein 2	Transcription factor involved in unfolded protein response (UPR). In the absence of endoplasmic reticulum (ER) stress, inserted into ER membranes, with N-terminal DNA-binding and transcription activation domains oriented toward the cytosolic face of the membrane. In response to ER stress, transported to the Golgi, where it is cleaved in a site-specific manner by resident proteases S1P/MBTPS1 and S2P/MBTPS2. The released N-terminal cytosolic domain is translocated to the nucleus to effect transcription of specific target genes. Plays a critical role in chondrogenesis by activating the transcription of SEC23A, which promotes the transport and secretion of cartilage matrix proteins, and possibly that of ER biogenesis-related genes. In a neuroblastoma cell line, protects cells from ER stress-induced death. In vitro activates transcription of target genes via direct binding to the CRE site.	loss of proteostasis	Homo sapiens	BBF2H7, a novel transmembrane bZIP transcription factor, is a new type of endoplasmic reticulum stress transducer	10.1128/MCB.01552-06	hsa04211	Longevity regulating pathway	64764
CREB3L3	Transcription Factor CREB-H	cyclic AMP-responsive element-binding protein 3-like protein 3	Transcription factor that may act during endoplasmic reticulum stress by activating unfolded protein response target genes. Activated in response to cAMP stimulation. In vitro, binds to the cAMP response element (CRE) and box-B element. Activates transcription through box-B element. Activates transcription through CRE. Seems to function synergistically with ATF6. In acute inflammatory response, may activate expression of acute phase response (APR) genes. May be involved in growth suppression.	loss of proteostasis	Homo sapiens	CREB-H: a novel mammalian transcription factor belonging to the CREB/ATF family and functioning via the box-B element with a liver-specific expression	10.1093/nar/29.10.2154	hsa04211	Longevity regulating pathway	84699
CREB3L4	Cyclic AMP-Responsive Element-Binding Protein 4	cyclic AMP-responsive element-binding protein 3-like protein 4	Transcriptional activator that may play a role in the unfolded protein response. Binds to the UPR element (UPRE) but not to CRE element. Preferentially binds DNA with to the consensus sequence 5'-T[GT]ACGT[GA][GT]-3' and has transcriptional activation activity from UPRE. Binds to NF-kappa-B site and has transcriptional activation activity from NF-kappa-B-containing regulatory elements.	loss of proteostasis	Homo sapiens	CREB4, a transmembrane bZip transcription factor and potential new substrate for regulation and cleavage by S1P	10.1091/mbc.e05-06-0500	hsa04211	Longevity regulating pathway	148327
CREB5	CREBPA	cyclic AMP-responsive element-binding protein 5	Binds to the cAMP response element and activates transcription.	others	Homo sapiens	Regulation of trans-activating capacity of CRE-BPa by phorbol ester tumor promoter TPA	PMID: 8378084	hsa04211	Longevity regulating pathway	9586
CREBBP	Histone Lysine Acetyltransferase CREBBP	CREB binding protein	Acetylates histones, giving a specific tag for transcriptional activation. Also acetylates non-histone proteins, like DDX21, FBL, IRF2, MAFG, NCOA3, POLR1E/PAF53 and FOXO1. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1. Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-ARNTL/BMAL1 and CLOCK-ARNTL/BMAL1 heterodimers.	others	Homo sapiens	Pokemon (FBI-1) interacts with Smad4 to repress TGF-β-induced transcriptional responses	10.1016/j.bbagrm.2014.12.008	hsa04066	HIF-1 signaling pathway	1387
CSF2RB	CD131; IL3RB	Colony Stimulating Factor 2 Receptor Subunit Beta	High affinity receptor for interleukin-3, interleukin-5 and granulocyte-macrophage colony-stimulating factor.	senescence-associated secretory phenotype	Homo sapiens	Senescence-associated-gene signature identifies genes linked to age, prognosis, and progression of human gliomas	10.1016/j.jgo.2014.08.003	unknown	Unknown	1439
CSNK1E	Casein Kinase I Isoform Epsilon	casein kinase 1, epsilon	Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Can phosphorylate a large number of proteins. Participates in Wnt signaling. Phosphorylates DVL1 and DVL2. Central component of the circadian clock. In balance with PP1, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. Controls PER1 and PER2 nuclear transport and degradation. Inhibits cytokine-induced granuloytic differentiation.	loss of proteostasis	Homo sapiens	Testing the circadian gene hypothesis in prostate cancer: a population-based case-control study	10.1158/0008-5472.CAN-09-0648	hsa04310	Wnt signaling pathway	1454
CTF1	Cardiotrophin-1	cardiotrophin 1	Induce cardiac myocyte hypertrophy in vitro. Binds to and activates the ILST/gp130 receptor.	others	Homo sapiens	Human cardiotrophin-1: protein and gene structure, biological and binding activities, and chromosomal localization	10.1006/cyto.1996.0026	hsa04630	JAK-STAT signaling pathway	1489
CTGF	IGFBP8; CCN2	connective tissue growth factor	The encoded protein plays a role in chondrocyte proliferation and differentiation, cell adhesion in many cell types, and is related to platelet-derived growth factor.	stem cell exhaustion	Homo sapiens	Expression of Connective Tissue Growth Factor, a Biomarker in Senescence of Human Diploid Fibroblasts, Is Up-Regulated by a Transforming Growth Factor-Beta-Mediated Signaling Pathway	10.1016/j.bbrc.2004.04.108	unknown	Unknown	1490
CTNNB1	beta-catenin; armadillo; CTNNB	catenin (cadherin-associated protein), beta 1, 88kDa	CTNNB1, also known as beta-catenin, is a member of the adherens junctions proteins, involved in epithelial layers that mediate adhesion between cells, cell communication, growth, embryogenesis, and wound healing.	altered intercellular communication	Homo sapiens	beta-Catenin Controls Hair Follicle Morphogenesis and Stem Cell Differentiation in the Skin	10.1016/s0092-8674(01)00336-1	hsa04310	Wnt signaling pathway	1499
CXCL1	GROa; MGSA	C-X-C Motif Chemokine Ligand 1	Has chemotactic activity for neutrophils. May play a role in inflammation and exerts its effects on endothelial cells in an autocrine fashion.	senescence-associated secretory phenotype	Homo sapiens	The Inflammatory Microenvironment of the Aging Prostate Facilitates Cellular Proliferation and Hypertrophy	10.1016/j.cyto.2008.05.012	hsa04064	NF-kappa B signaling pathway	2919
CXCL12	SDF-1a; SDF-1b	C-X-C Motif Chemokine Ligand 12	Chemoattractant active on T-lymphocytes and monocytes but not neutrophils. Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions and chemotaxis.	senescence-associated secretory phenotype	Homo sapiens	The Inflammatory Microenvironment of the Aging Prostate Facilitates Cellular Proliferation and Hypertrophy	10.1016/j.cyto.2008.05.012	hsa04064	NF-kappa B signaling pathway	6387
CXCL2	MIP-2a; MIP2A	C-X-C Motif Chemokine Ligand 2	Produced by activated monocytes and neutrophils and expressed at sites of inflammation.	senescence-associated secretory phenotype	Homo sapiens	The Inflammatory Microenvironment of the Aging Prostate Facilitates Cellular Proliferation and Hypertrophy	10.1016/j.cyto.2008.05.012	hsa04064	NF-kappa B signaling pathway	2920
CXCL5	ENA-78; SCYB5	C-X-C Motif Chemokine Ligand 5	Involved in neutrophil activation.	senescence-associated secretory phenotype	Homo sapiens	The Inflammatory Microenvironment of the Aging Prostate Facilitates Cellular Proliferation and Hypertrophy	10.1016/j.cyto.2008.05.012	unknown	Unknown	6374
CXCL6	SCYB6; GCP2	C-X-C Motif Chemokine Ligand 6	Chemotactic for neutrophil granulocytes. Signals through binding and activation of its receptors (CXCR1 and CXCR2).	senescence-associated secretory phenotype	Homo sapiens	The Inflammatory Microenvironment of the Aging Prostate Facilitates Cellular Proliferation and Hypertrophy	10.1016/j.cyto.2008.05.012	unknown	Unknown	6372
CXCL8	LYNAP; SCYB8	C-X-C Motif Chemokine Ligand 8	IL-8 is a chemotactic factor that attracts neutrophils, basophils, and T-cells, but not monocytes. It is also involved in neutrophil activation. It is released from several cell types in response to an inflammatory stimulus.	senescence-associated secretory phenotype	Homo sapiens	Activation profile of CXCL8-stimulated neutrophils and aging	10.1016/j.cyto.2013.01.016	hsa04218	Cellular senescence	3576
CYCS	THC4	Cytochrome C	Plays a role in apoptosis. Suppression of the anti-apoptotic members or activation of the pro-apoptotic members of the Bcl-2 family leads to altered mitochondrial membrane permeability resulting in release of cytochrome c into the cytosol. Binding of cytochrome c to Apaf-1 triggers the activation of caspase-9, which then accelerates apoptosis by activating other caspases.	cellular senescence	Homo sapiens	SQSTM1/p62 and PPARGC1A/PGC-1alpha at the interface of autophagy and vascular senescence	10.1080/15548627.2019.1659612	hsa04115	p53 signaling pathway	54205
DBN1	D0S117E	drebrin 1	DBN1 is thought to be involved in neuronal growth.	loss of proteostasis	Homo sapiens	Coordinated gene expression of neuroinflammatory and cell signaling markers in dorsolateral prefrontal cortex during human brain development and aging	10.1371/journal.pone.0110972	unknown	Unknown	1627
DCTN1	DAP-150	Dynactin Subunit 1	DCTN1 plays a key role in dynein-mediated retrograde transport of vesicles and organelles along microtubules by recruiting and tethering dynein to microtubules. Binds to both dynein and microtubules providing a link between specific cargos, microtubules and dynein. Essential for targeting dynein to microtubule plus ends, recruiting dynein to membranous cargos and enhancing dynein processivity (the ability to move along a microtubule for a long distance without falling off the track). Can also act as a brake to slow the dynein motor during motility along the microtubule (PubMed:25185702). Can regulate microtubule stability by promoting microtubule formation, nucleation and polymerization and by inhibiting microtubule catastrophe in neurons. Inhibits microtubule catastrophe by binding both to microtubules and to tubulin, leading to enhanced microtubule stability along the axon (PubMed:23874158). Plays a role in metaphase spindle orientation (PubMed:22327364). Plays a role in centriole cohesion and subdistal appendage organization and function. Its recruitment to the centriole in a KIF3A-dependent manner is essential for the maintenance of centriole cohesion and the formation of subdistal appendage. Also required for microtubule anchoring at the mother centriole (PubMed:23386061). Plays a role in primary cilia formation.	others	Homo sapiens	Dynactin pathway-related gene expression is altered by aging, but not by vitrification	10.1016/j.reprotox.2019.06.011	H00058	Amyotrophic lateral sclerosis (ALS)	1639
DDIT3	CHOP10; GADD153; CHOP	DNA-damage-inducible transcript 3	DDIT3 prevents transcription in response to DNA damage.  It also appears to be related to apoptosis.	genomic instability	Homo sapiens	Expression of the Pro-Apoptotic Gene gadd153/chop Is Elevated in Liver With Aging and Sensitizes Cells to Oxidant Injury	10.1074/jbc.M300677200	hsa04010	MAPK signaling pathway	1649
DDX58	RIG-I; RIG1; RIGI	DExD/H-box helicase 58	Aging compromises both the primary and secondary RIG-I signaling pathways that govern expression of type I IFN genes, thereby impairing antiviral resistance to IAV.	NF-κB related gene	Homo sapiens	Aging impairs both primary and secondary RIG-I signaling for interferon induction in human monocytes	10.1126/scisignal.aan2392	hsa04064	NF-kappa B signaling pathway	23586
DGAT1	Diglyceride Acyltransferase	diacylglycerol O-acyltransferase 1	Catalyzes the terminal and only committed step in triacylglycerol synthesis by using diacylglycerol and fatty acyl CoA as substrates. In contrast to DGAT2 it is not essential for survival. May be involved in VLDL (very low density lipoprotein) assembly. In liver, plays a role in esterifying exogenous fatty acids to glycerol. Functions as the major acyl-CoA retinol acyltransferase (ARAT) in the skin, where it acts to maintain retinoid homeostasis and prevent retinoid toxicity leading to skin and hair disorders.	others	Homo sapiens	Acyl coenzyme A dependent retinol esterification by acyl coenzyme A: diacylglycerol acyltransferase 1.	10.1016/j.bbalip.2005.09.003	unknown	Unknown	8694
DLAT	PBC; E2	dihydrolipoamide S-acetyltransferase	The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.	mitochondrial dysfunction	Homo sapiens	Proteomics and metabolomics identify molecular mechanisms of aging potentially predisposing for chronic lymphocytic leukemia	10.1074/mcp.RA117.000425	unknown	Unknown	1737
DLL3	SCDO1	delta-like 3 (Drosophila)	DLL3 has been linked to development and neurogenesis.	stem cell exhaustion	Homo sapiens	Novel Mutations in DLL3, a Somitogenesis Gene Encoding a Ligand for the Notch Signalling Pathway, Cause a Consistent Pattern of Abnormal Vertebral Segmentation in Spondylocostal Dysostosis	10.1136/jmg.40.5.333	hsa04330	Notch signaling pathway	10683
E2F1	RBP3	E2F transcription factor 1	Transcription activator that binds DNA cooperatively with DP proteins through the E2 recognition site, 5'-TTTC[CG]CGC-3' found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication.	genomic instability	Homo sapiens	E2F transcription factor action, regulation and possible role in human cancer	10.1046/j.1365-2184.1997.00085.x	hsa04218	Cellular senescence	1869
EDARADD	ECTD11B; ED3; EDA3	EDAR associated death domain	The methylation of site--in the promoters of the EDARADD genes--is linear with age over a range of five decades, which could be a model to estimate the age of a person, based on a biological sample alone.	NF-κB related gene	Homo sapiens	Epigenetic predictor of age	10.1371/journal.pone.0014821	hsa04064	NF-kappa B signaling pathway	128178
EEF1A1	EF1A; EEF1A; LENG7	eukaryotic translation elongation factor 1 alpha 1	EEF1A1 is involved in the binding of tRNA to ribosomes during protein synthesis. This protein promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis. With PARP1 and TXK, forms a complex that acts as a T helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production.	genomic instability	Homo sapiens	Nerve growth factor specifically stimulates translation of eukaryotic elongation factor 1A-1 (eEF1A-1) mRNA by recruitment to polyribosomes in PC12 cells	10.1074/jbc.M111782200	unknown	Unknown	1915
EEF1E1	minoacyl TRNA Synthetase Complex-Interacting Multifunctional Protein 3	eukaryotic translation elongation factor 1 epsilon 1	Positive modulator of ATM response to DNA damage.	genomic instability	Homo sapiens	Dissection of the structural organization of the aminoacyl-tRNA synthetase complex	10.1074/jbc.M809636200	unknown	Unknown	9521
EEF2	EEF-2; EF2	eukaryotic translation elongation factor 2	Age-dependent changes to EEF2 in rats, which could account for the decline in protein synthesis in old animals.	loss of proteostasis	Homo sapiens	Elongation factor 2 diphthamide is critical for translation of two IRES-dependent protein targets, XIAP and FGF2, under oxidative stress conditions	10.1016/j.freeradbiomed.2013.10.015	unknown	Unknown	1938
EFEMP1	EGF Containing Fibulin Extracellular Matrix Protein 1	EGF containing fibulin-like extracellular matrix protein 1	Binds EGFR, the EGF receptor, inducing EGFR autophosphorylation and the activation of downstream signaling pathways. May play a role in cell adhesion and migration. May function as a negative regulator of chondrocyte differentiation. In the olfactory epithelium, it may regulate glial cell migration, differentiation and the ability of glial cells to support neuronal neurite outgrowth.	altered intercellular communication	Homo sapiens	EFEMP1 binds the EGF receptor and activates MAPK and Akt pathways in pancreatic carcinoma cells	https://doi.org/10.1515/BC.2009.140	unknown	Unknown	2202
EGF	HOMG4; URG	epidermal growth factor	EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture.	cellular senescence	Homo sapiens	EGF/EGFR Upregulates and Cooperates With Netrin-4 to Protect Glioblastoma Cells From DNA Damage-Induced Senescence	10.1186/s12885-018-5056-4	hsa04010	MAPK signaling pathway	1950
EGFR	ERBB1	epidermal growth factor receptor	Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses.	cellular senescence	Homo sapiens	Mechanisms of Skin Aging Induced by EGFR Inhibitors	10.1007/s00520-016-3254-7	hsa04010	MAPK signaling pathway	1956
EGR1	ZNF225; AT225	early growth response 1	Transcriptional regulator. Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3'(EGR-site) in the promoter region of target genes.	cellular senescence	Homo sapiens	Early Life Stress and Epigenetics in Late-onset Alzheimer's Dementia: A Systematic Review	10.2174/1389202919666171229145156	hsa04912	GnRH signaling pathway	1958
EHMT1	Histone H3-K9 Methyltransferase 5	histone-lysine N-methyltransferase EHMT1	Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. During G0 phase, it probably contributes to silencing of MYC- and E2F-responsive genes, suggesting a role in G0/G1 transition in cell cycle. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53.	epigenetic alterations	Homo sapiens	A complex with chromatin modifiers that occupies E2F- and Myc-responsive genes in G0 cells	10.1126/science.1069861	hsa04211	Longevity regulating pathway	79813
EHMT2	Histone-Lysine N-Methyltransferase EHMT2	euchromatic histone lysine methyltransferase 2	Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also mediates monomethylation of 'Lys-56' of histone H3 (H3K56me1) in G1 phase, leading to promote interaction between histone H3 and PCNA and regulating DNA replication. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. May also methylate histone H1. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53. Also methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1, ERCC6, KLF12 and itself.	epigenetic alterations	Homo sapiens	The G9a gene in the human major histocompatibility complex encodes a novel protein containing ankyrin-like repeats	10.1042/bj2900811	hsa04211	Longevity regulating pathway	10919
EIF4E	MRNA Cap-Binding Protein	eukaryotic translation initiation factor 4E	Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures. Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit mediates the binding to the mRNA cap.	others	Homo sapiens	Translational homeostasis via the mRNA cap-binding protein, eIF4E	10.1016/j.molcel.2012.04.004	hsa04211	Longevity regulating pathway	1977
EIF4E1B	Eukaryotic Translation Initiation Factor 4E Family Member 1B	eukaryotic translation initiation factor 4E type 1B	Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structure.	others	Homo sapiens	Phylogenetic analysis of eIF4E-family members	10.1186/1471-2148-5-48	hsa04211	Longevity regulating pathway	253314
EIF4E2	MRNA Cap-Binding Protein Type 3	eukaryotic translation initiation factor 4E type 2	Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation. Acts as a repressor of translation initiation. In contrast to EIF4E, it is unable to bind eIF4G (EIF4G1, EIF4G2 or EIF4G3), suggesting that it acts by competing with EIF4E and block assembly of eIF4F at the cap.	others	Homo sapiens	Cloning and characterization of 4EHP, a novel mammalian eIF4E-related cap-binding protein	10.1074/jbc.273.21.13104	hsa04211	Longevity regulating pathway	9470
EIF4EBP1	Eukaryotic Translation Initiation Factor 4E-Binding Protein 1	eukaryotic translation initiation factor 4E-binding protein 1	Repressor of translation initiation that regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repress translation. In contrast, hyperphosphorylated form dissociates from EIF4E, allowing interaction between EIF4G1/EIF4G3 and EIF4E, leading to initiation of translation. Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways.	others	Homo sapiens	Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function	10.1038/371762a0	hsa04211	Longevity regulating pathway	1978
EIF5A2	Eukaryotic Initiation Factor 5A	eukaryotic translation initiation factor 5A2	mRNA-binding protein involved in translation elongation. Has an important function at the level of mRNA turnover, probably acting downstream of decapping. Involved in actin dynamics and cell cycle progression, mRNA decay and probably in a pathway involved in stress response and maintenance of cell wall integrity. Functions as a regulator of apoptosis. Mediates effects of polyamines on neuronal process extension and survival. May play an important role in brain development and function, and in skeletal muscle stem cell differentiation.	loss of proteostasis	Homo sapiens	Identification and characterization of eukaryotic initiation factor 5A-2	10.1046/j.1432-1033.2003.03806.x	unknown	Unknown	56648
ELN	WBS; WS; SVAS	elastin	ELN is structural protein that may be related to arterial morphogenesis.	altered intercellular communication	Homo sapiens	Multisystem Study of 20 Older Adults With Williams Syndrome	10.1002/ajmg.a.30400	hsa04151	PI3K-Akt signaling pathway	2006
EMD	STA; LEMD5	emerin	The functions of EMD in the nuclear lamina may indicate a role for EMD in ageing and have roles in chromatin organization, gene regulation and signal transduction.	others	Homo sapiens	The Nuclear Lamina Comes of Age	10.1038/nrm1550	unknown	Unknown	2010
ENO1	ENO1L1; HEL-S-17	enolase 1	Glycolytic enzyme the catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate. In addition to glycolysis, involved in various processes such as growth control, hypoxia tolerance and allergic responses.	others	Homo sapiens	Alcohol drinking exacerbates neural and behavioral pathology in the 3xTg-AD mouse model of Alzheimer's disease	10.1016/bs.irn.2019.10.017	hsa04066	HIF-1 signaling pathway	2023
ENO2	HEL-S-279; NSE	enolase 2	Has neurotrophic and neuroprotective properties on a broad spectrum of central nervous system (CNS) neurons.	others	Homo sapiens	Alcohol drinking exacerbates neural and behavioral pathology in the 3xTg-AD mouse model of Alzheimer's disease	10.1016/bs.irn.2019.10.017	hsa04066	HIF-1 signaling pathway	2026
EP300	p300; KAT3B	E1A binding protein p300	EP300 mediates many transcriptional events including DNA repair.EP300 has been associated with several other proteins that may be involved in ageing, such as WRN.	genomic instability	Homo sapiens	DNA Damage-Induced Translocation of the Werner Helicase Is Regulated by Acetylation	10.1074/jbc.M210479200	hsa04935	Growth hormone synthesis, secretion and action	2033
EPOR	EPO-R	erythropoietin receptor	Receptor for erythropoietin. Mediates erythropoietin-induced erythroblast proliferation and differentiation. Upon EPO stimulation, EPOR dimerizes triggering the JAK2/STAT5 signaling cascade.	cellular senescence	Homo sapiens	Erythropoietin Signaling Increases Choroidal Macrophages and Cytokine Expression, and Exacerbates Choroidal Neovascularization	10.1038/s41598-018-20520-z	hsa04630	JAK-STAT signaling pathway	2057
EPS8	Epidermal Growth Factor Receptor Kinase Substrate 8	epidermal growth factor receptor pathway substrate 8	Stimulates guanine exchange activity of SOS1. May play a role in membrane ruffling and remodeling of the actin cytoskeleton. In the cochlea, is required for stereocilia maintenance in adult hair cells.	others	Homo sapiens	The eps8 family of proteins links growth factor stimulation to actin reorganization generating functional redundancy in the Ras/Rac pathway	10.1091/mbc.E03-06-0427	unknown	Unknown	2059
ERBB2	HER2; NGL	erb-b2 receptor tyrosine kinase 2	Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone.	others	Homo sapiens	Premature Senescence Is a Primary Fail-Safe Mechanism of ERBB2-driven Tumorigenesis in Breast Carcinoma Cells	PMID: 15705882	hsa04010	MAPK signaling pathway	2064
ERCC1	RAD10	excision repair cross-complementation group 1	ERCC1 has a role in DNA repair in association with the other ERCC proteins.	genomic instability	Homo sapiens	Formation of a Ternary Complex by Human XPA, ERCC1, and ERCC4(XPF) Excision Repair Proteins	10.1073/pnas.91.11.5017	unknown	Unknown	2067
ERCC2	CXPD; XPD	excision repair cross-complementation group 2	ATP-dependent 5'-3' DNA helicase, component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II.	genomic instability	Homo sapiens	The Involvement of ERCC2/XPD and ERCC6/CSB Wild Type Alleles in Protection Against Aging and Cancer	10.2174/1874609810666170707101548	unknown	Unknown	2068
ERCC3	XPB; BTF2; RAD25	excision repair cross-complementation group 3	ERCC3 is an ATP-dependent 3'-5' directed DNA helicase involved in basal RNA transcription and the nucleotide excision repair (NER) pathway.	genomic instability	Homo sapiens	Telomere Attrition and Genomic Instability in Xeroderma Pigmentosum Type-B Deficient Fibroblasts Under Oxidative Stress	10.1111/j.1582-4934.2009.00945.x	unknown	Unknown	2071
ERCC4	ERCC Excision Repair 4; Endonuclease Catalytic Subunit	excision repair cross-complementation group 4	Catalytic component of a structure-specific DNA repair endonuclease responsible for the 5-prime incision during DNA repair. Involved in homologous recombination that assists in removing interstrand cross-link.	genomic instability	Homo sapiens	Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair	10.1016/j.cell.2009.06.030	unknown	Unknown	2072
ERCC5	ERCM2; XPGC	excision repair cross-complementation group 5	ERCC5 may reduce endogenous DNA damage and attend therapy for human progeroid genome instability syndromes.	genomic instability	Homo sapiens	Human xeroderma pigmentosum group G gene encodes a DNA endonuclease	10.1093/nar/22.16.3312	unknown	Unknown	2073
ERCC6	CSB; RAD26; ARMD5	excision repair cross-complementation group 6	Mutant for ERCC6 and XPA die before weaning and display some signs of premature ageing included stunted growth, neurological dysfunction, retinal degeneration, cachexia, and kyphosis.	others	Homo sapiens	Cockayne syndrome group B cellular and biochemical functions	10.1086/380399	unknown	Unknown	2074
ERCC8	CKN1; CSA	excision repair cross-complementation group 8	Substrate-recognition component of the CSA complex, a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex, involved in transcription-coupled nucleotide excision repair.	genomic instability	Homo sapiens	Two Novel Heterozygous Mutations in ERCC8 Cause Cockayne Syndrome in a Chinese Patient	10.1016/j.pediatrneurol.2015.06.006	unknown	Unknown	1161
ESR1	NR3A1; Era; ESR	estrogen receptor 1	ESR1 is a transcription factor that mediates the actions of estrogen. Mice without ESR1 were infertile and showed a variety of changes.	genomic instability	Homo sapiens	Age-dependent Methylation of ESR1 Gene in Prostate Cancer	10.1016/j.bbrc.2004.06.164	unknown	Unknown	2099
FADS1	D5D; FADS6; FADSD5	fatty acid desaturase 1	Long-chain polyunsaturated fatty acids (LCPUFAs) biosynthetic capacity is regulated by FADS1 polymorphisms and decreased by aging in FADS1 C allele carriers.	others	Homo sapiens	Aging and FADS1 polymorphisms decrease the biosynthetic capacity of long-chain PUFAs: A human trial using [U- 13 C]linoleic acid	10.1016/j.plefa.2019.07.003	unknown	Unknown	3992
FAS	CD95; APO-1; FAS1	fas cell surface death receptor	Fas-mediated apoptosis has a role in aging of human epidermis. Epidermal Fas expression and apoptosis are increased in aged human skin.	others	Homo sapiens	Aging of Human Epidermis: Reversal of Aging Changes Correlates With Reversal of Keratinocyte Fas Expression and Apoptosis	10.1093/gerona/59.5.b411	hsa04115	p53 signaling pathway	355
FBP1	FBP	fructose-bisphosphatase 1	Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis. Plays a role in regulating glucose sensing and insulin secretion of pancreatic beta-cells.	others	Homo sapiens	Common and cell type-specific responses of human cells to mitochondrial dysfunction	10.1016/j.yexcr.2004.09.006	hsa04910	Insulin signaling pathway	2203
FEN1	FEN-1; MF1; RAD2	flap structure-specific endonuclease 1	Involved in DNA processing, FEN-1 removes 5' overhanging flaps in DNA repair and processes the 5' ends of Okazaki fragments in lagging strand DNA synthesis.	genomic instability	Homo sapiens	Structure of the DNA Repair and Replication Endonuclease and Exonuclease FEN-1: Coupling DNA and PCNA Binding to FEN-1 Activity	10.1016/s0092-8674(00)81789-4	unknown	Unknown	2237
FGF21	FGF-21	fibroblast growth factor 21	Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB.	deregulated nutrient sensing	Homo sapiens	FGF-21 as a novel metabolic regulator	10.1172/JCI23606	hsa04010	MAPK signaling pathway	26291
FGF23	Tumor-Derived Hypophosphatemia Inducing Factor	fibroblast growth factor 23	Regulator of phosphate homeostasis. Inhibits renal tubular phosphate transport by reducing SLC34A1 levels. Upregulates EGR1 expression in the presence of KL. Acts directly on the parathyroid to decrease PTH secretion. Regulator of vitamin-D metabolism. Negatively regulates osteoblast differentiation and matrix mineralization.	others	Homo sapiens	FGF-23 inhibits renal tubular phosphate transport and is a PHEX substrate	https://doi.org/10.1006/bbrc.2001.5084	hsa04010	MAPK signaling pathway	8074
FGF7	HBGF-7; KGF	fibroblast growth factor 7	Hominis Placenta (HP) treatment significantly increased the expression of FGF-7, which plays pivotal roles to maintain anagen phase both protein and mRNA levels.	senescence-associated secretory phenotype	Homo sapiens	Hominis Placenta facilitates hair re-growth by upregulating cellular proliferation and expression of fibroblast growth factor-7	10.1186/s12906-016-1180-3	hsa04010	MAPK signaling pathway	2252
FGFR1	CEK; FLG; N-SAM	fibroblast growth factor receptor 1	FGFR1 is the receptor of the fibroblast growth factor.	altered intercellular communication	Homo sapiens	Attenuation of FGF Signalling in   Beta-Cells Leads to Diabetes	10.1038/35048589	hsa04010	MAPK signaling pathway	2260
FGFR3	JTK4	Fibroblast Growth Factor Receptor 3	Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis. Plays an essential role in the regulation of chondrocyte differentiation, proliferation and apoptosis, and is required for normal skeleton development. Regulates both osteogenesis and postnatal bone mineralization by osteoblasts. Promotes apoptosis in chondrocytes, but can also promote cancer cell proliferation. Required for normal development of the inner ear. Phosphorylates PLCG1, CBL and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Plays a role in the regulation of vitamin D metabolism. Mutations that lead to constitutive kinase activation or impair normal FGFR3 maturation, internalization and degradation lead to aberrant signaling. Over-expressed or constitutively activated FGFR3 promotes activation of PTPN11/SHP2, STAT1, STAT5A and STAT5B. Secreted isoform 3 retains its capacity to bind FGF1 and FGF2 and hence may interfere with FGF signaling.	others	Homo sapiens	Hepatic gene body hypermethylation is a shared epigenetic signature of murine longevity	10.1371/journal.pgen.1007766	hsa04010	MAPK signaling pathway	2261
FLT1	VEGFR1; FLT	fms-related tyrosine kinase 1	It is involved in signalling cascade.	epigenetic alterations	Homo sapiens	Aging and Orchidectomy Modulate Expression of VEGF Receptors (Flt-1 and Flk-1) on Corpus Cavernosum of the Rat	10.1196/annals.1354.020	unknown	Unknown	2321
FOS	P55	FBJ murine osteosarcoma viral oncogene homolog	Nuclear phosphoprotein which forms a tight but non-covalently linked complex with the JUN/AP-1 transcription factor. In the heterodimer, FOS and JUN/AP-1 basic regions each seems to interact with symmetrical DNA half sites.	cellular senescence	Homo sapiens	An altered repertoire of fos/jun (AP-1) at the onset of replicative senescence	10.1016/0014-4827(92)90415-5	hsa04935	Growth hormone synthesis, secretion and action	2353
FOXL2	PINTO	Forkhead Box Protein L2	Transcriptional regulator. Critical factor essential for ovary differentiation and maintenance, and repression of the genetic program for somatic testis determination. Prevents trans-differentiation of ovary to testis through transcriptional repression of the Sertoli cell-promoting gene SOX9 (By similarity). Has apoptotic activity in ovarian cells. Suppresses ESR1-mediated transcription of PTGS2/COX2 stimulated by tamoxifen (By similarity). Is a regulator of CYP19 expression (By similarity). Participates in SMAD3-dependent transcription of FST via the intronic SMAD-binding element (By similarity). Is a transcriptional repressor of STAR. Activates SIRT1 transcription under cellular stress conditions. Activates transcription of OSR2.	others	Homo sapiens	Transcriptional factor FOXL2 interacts with DP103 and induces apoptosis.	10.1016/j.bbrc.2005.08.184	unknown	Unknown	668
FOXM1	HFH-11; HNF-3	forkhead box M1	Increased Foxm1b levels are essential for GH to stimulate hepatocyte proliferation. Increased expression of FOXM1 in old mice restored hepatocyte proliferation to levels found in young animals.	deregulated nutrient sensing	Homo sapiens	FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence	10.1038/s41467-018-05258-6	hsa04218	Cellular senescence	2305
FOXO1	FKH1; FKHR; FOXO1A	forkhead box O1	FOXO1 negatively regulates skeletal muscle mass and type I fiber gene expression and leads to impaired skeletal muscle function.	others	Homo sapiens	Fox's in development and disease	10.1016/S0168-9525(03)00111-2	hsa04211	Longevity regulating pathway	2308
FOXO3	AF6q21; FOXO2; FKHRL1	forkhead box O3	A transcription factor of the Fox family, FOXO3, is crucial in development.	others	Homo sapiens	Fox's in Development and Disease	10.1016/S0168-9525(03)00111-2	hsa04211	Longevity regulating pathway	2309
FOXO4	AFX1; MLLT7	forkhead box O4	FOXO4 plays a role in development and in insulin (INS) signalling.	deregulated nutrient sensing	Homo sapiens	Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging	10.1016/j.cell.2017.02.031	hsa04068	FoxO signaling pathway	4303
GAPDH	G3PD	glyceraldehyde-3-phosphate dehydrogenase	Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively. Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis.	others	Homo sapiens	Ishemia-reperfusion enhances GAPDH nitration in aging skeletal muscle	10.18632/aging.100394	hsa04066	HIF-1 signaling pathway	2597
GCK	HHF3; HKIV	glucokinase	Catalyzes the phosphorylation of hexose, such as D-glucose, D-fructose and D-mannose, to hexose 6-phosphate.	others	Homo sapiens	GCK gene-body hypomethylation is associated with the risk of coronary heart disease	10.1155/2014/151723	hsa04910	Insulin signaling pathway	2645
GCLC	Gamma-Glutamylcysteine Synthetase	glutamate-cysteine ligase, catalytic subunit	Glutamate-cysteine ligase, also known as gamma-glutamylcysteine synthetase is the first rate-limiting enzyme of glutathione synthesis. The enzyme consists of two subunits, a heavy catalytic subunit and a light regulatory subunit. This locus encodes the catalytic subunit, while the regulatory subunit is derived from a different gene located on chromosome 1p22-p21. Mutations at this locus have been associated with hemolytic anemia due to deficiency of gamma-glutamylcysteine synthetase and susceptibility to myocardial infarction.	loss of proteostasis	Homo sapiens	Association of polymorphisms of glutamate-cystein ligase and microsomal triglyceride transfer protein genes in non-alcoholic fatty liver disease	10.1111/j.1440-1746.2009.06001.x	unknown	Unknown	2729
GCLM	Gamma-Glutamylcysteine Synthetase Regulatory Subunit	glutamate-cysteine ligase, modifier subunit	Glutamate-cysteine ligase, also known as gamma-glutamylcysteine synthetase, is the first rate limiting enzyme of glutathione synthesis. The enzyme consists of two subunits, a heavy catalytic subunit and a light regulatory subunit. Gamma glutamylcysteine synthetase deficiency has been implicated in some forms of hemolytic anemia. Alternative splicing results in multiple transcript variants encoding different isoforms.	loss of proteostasis	Homo sapiens	Structure, function, and post-translational regulation of the catalytic and modifier subunits of glutamate cysteine ligase	10.1016/j.mam.2008.08.009	unknown	Unknown	2730
GDF11	Bone Morphogenetic Protein 11	growth differentiation factor 11	Secreted signal that acts globally to specify positional identity along the anterior/posterior axis during development. May play critical roles in patterning both mesodermal and neural tissues and in establishing the skeletal pattern. Signals through activin receptors type-2, ACVR2A and ACVR2B, and activin receptors type-1, ACVR1B, ACVR1C and TGFBR1 leading to the phosphorylation of SMAD2 and SMAD3.	others	Homo sapiens	Structural Basis for Potency Differences Between GDF8 and GDF11	10.1186/s12915-017-0350-1	unknown	Unknown	10220
GDF15	MIC1; NAG-1; PDF	growth differentiation factor 15	Both the intracellular GDF15 and the circulating mature GDF15 are implicated in biological processes, such as energy homeostasis and body weight regulation.	senescence-associated secretory phenotype	Homo sapiens	Growth differentiation factor 15 (GDF15): A survival protein with therapeutic potential in metabolic diseases	10.1016/j.pharmthera.2019.02.008	unknown	Unknown	9518
GH1	GH; IGHD2	growth hormone 1	It plays an important role in growth control. Its major role in stimulating body growth is to stimulate the liver and other tissues to secrete IGF-1.	cellular senescence	Homo sapiens	Growth hormone secretion is diminished and tightly controlled in humans enriched for familial longevity	10.1111/acel.12519	hsa04935	Growth hormone synthesis, secretion and action	2688
GHR	GHBP; GHIP	growth hormone receptor	Receptor for pituitary gland growth hormone involved in regulating postnatal body growth. On ligand binding, couples to the JAK2/STAT5 pathway.	loss of proteostasis	Homo sapiens	Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans	10.1126/scitranslmed.3001845	hsa04935	Growth hormone synthesis, secretion and action	2690
GHRH	GHRF; GRF	growth hormone releasing hormone	GRF is released by the hypothalamus and acts on the adenohypophyse to stimulate the secretion of growth hormone.	loss of proteostasis	Homo sapiens	In vivo semiquantification of hypothalamic growth hormone-releasing hormone (GHRH) output in humans: evidence for relative GHRH deficiency in aging	10.1210/jcem.84.10.6063	hsa04935	Growth hormone synthesis, secretion and action	2691
GHRHR	GRFR	growth hormone releasing hormone receptor	Receptor for GRF, coupled to G proteins which activate adenylyl cyclase. Stimulates somatotroph cell growth, growth hormone gene transcription and growth hormone secretion.	deregulated nutrient sensing	Homo sapiens	Familial Dwarfism Due to a Novel Mutation of the Growth Hormone-Releasing Hormone Receptor Gene	10.1210/jcem.84.3.5599	hsa04935	Growth hormone synthesis, secretion and action	2692
GPX1	Glutathione Peroxidase 1; GSHPX1; GPXD	glutathione peroxidase 1	Overexpression of GPX1 in mice results in insulin (INS) resistance and obesity.	deregulated nutrient sensing	Homo sapiens	Association of GPX1 and GPX4 polymorphisms with episodic memory and Alzheimer's disease	10.1016/j.neulet.2017.12.026	unknown	Unknown	2876
GPX4	Phospholipid Hydroperoxide Glutathione Peroxidase	glutathione peroxidase 4	Essential antioxidant peroxidase that directly reduces phospholipid hydroperoxide even if they are incorporated in membranes and lipoproteins. Can also reduce fatty acid hydroperoxide, cholesterol hydroperoxide and thymine hydroperoxide. Plays a key role in protecting cells from oxidative damage by preventing membrane lipid peroxidation. Required to prevent cells from ferroptosis, a non-apoptotic cell death resulting from an iron-dependent accumulation of lipid reactive oxygen species. Plays a role in a primary T-cell response to viral and parasitic infection by protecting T-cells from ferroptosis and by supporting T-cell expansion. Plays a role of glutathione peroxidase in platelets in the arachidonic acid metabolism.	others	Homo sapiens	Regulation of Ferroptotic Cancer Cell Death by GPX4	10.1016/j.cell.2013.12.010	unknown	Unknown	2879
GRB2	NCKAP2	growth factor receptor-bound protein 2	GRB2 has a role as a signal transducer of many pathways, including pathways and genes previously related to ageing such as INS/IGF1 signalling and SHC1.	deregulated nutrient sensing	Homo sapiens	Feedback between p21 and reactive oxygen production is necessary for cell senescence	10.1038/msb.2010.5	hsa04910	Insulin signaling pathway	2885
GRIA2	GluA2	Glutamate Ionotropic Receptor AMPA Type Subunit 2	Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate. Through complex formation with NSG1, GRIP1 and STX12 controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting.	others	Homo sapiens	Epigenetic-aging-signature to determine age in different tissues	10.18632/aging.100395	hsa04024	cAMP signaling pathway	2891
GRN	PC Cell-Derived Growth Factor	granulin	Secreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation. Regulates protein trafficking to lysosomes and, also the activity of lysosomal enzymes. Facilitates also the acidification of lysosomes, causing degradation of mature CTSD by CTSB. In addition, functions as wound-related growth factor that acts directly on dermal fibroblasts and endothelial cells to promote division, migration and the formation of capillary-like tubule structures. Also promotes epithelial cell proliferation by blocking TNF-mediated neutrophil activation preventing release of oxidants and proteases. Moreover, modulates inflammation in neurons by preserving neurons survival, axonal outgrowth and neuronal integrity.	others	Homo sapiens	GRN variability contributes to sporadic frontotemporal lobar degeneration	10.3233/JAD-2010-1225	unknown	Unknown	2896
GSK3A	Glycogen Synthase Kinase-3 Alpha	glycogen synthase kinase 3 alpha	Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), CTNNB1/beta-catenin, APC and AXIN1. Requires primed phosphorylation of the majority of its substrates. Contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. Regulates glycogen metabolism in liver, but not in muscle. May also mediate the development of insulin resistance by regulating activation of transcription factors. Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions, leading to activate KAT5/TIP60 acetyltransferase activity and promote acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer.	deregulated nutrient sensing	Homo sapiens	Glycogen synthase kinase-3: properties, functions, and regulation	10.1021/cr000110o	unknown	Unknown	2931
GSK3B	Glycogen Synthase Kinase 3 Beta; Serine/Threonine-Protein Kinase GSK3B	glycogen synthase kinase 3 beta	Adult overexpression of GSK3B in the brain of   resulted in neurodegeneration. GSK-3beta has been postulated to mediate Alzheimer's disease tau hyperphosphorylation, beta-amyloid-induced neurotoxicity and presenilin-1 mutation pathogenic effects.	others	Homo sapiens	Early Life Stress and Epigenetics in Late-onset Alzheimer's Dementia: A Systematic Review	10.2174/1389202919666171229145156	hsa04910	Insulin signaling pathway	2932
GSR	Glutathione-Disulfide Reductase; GRase; GRD1	glutathione reductase	GSR is involved in redox regulation and oxidative defence.	others	Homo sapiens	Loss of glutathione redox homeostasis impairs proteostasis by inhibiting autophagy-dependent protein degradation	10.1038/s41418-018-0270-9	unknown	Unknown	2936
GSS	GSHS; GSH-S; Glutathione Synthase	glutathione synthetase	Mutations in the human GSS gene cause 5-oxoprolinuria. GSS is involved in redox regulation.	others	Homo sapiens	Mutations in the Glutathione Synthetase Gene Cause 5-oxoprolinuria	10.1038/ng1196-361	unknown	Unknown	2937
GSTA4	GTA4	glutathione S-transferase alpha 4	It is involved in oxidative protection as well as the removal of toxins and harmful metabolic by-products.	altered intercellular communication	Homo sapiens	Glutathione S-transferase Isoenzymatic Response to Aging in Rat Cerebral Cortex and Cerebellum	10.1016/s0197-4580(02)00139-2	unknown	Unknown	2941
GSTP1	GSTP; FAEES3; GST3	glutathione S-transferase pi 1	It is involved in oxidative protection, extend lifespan.	epigenetic alterations	Homo sapiens	DNA methylation in repeat negative prostate biopsies as a marker of missed prostate cancer	10.1186/s13148-019-0746-6	unknown	Unknown	2950
GTF2H2	BTF2; TFIIH; BTF2P44	general transcription factor IIH, polypeptide 2, 44kDa	Transcription factor II H interacts with a variety of factors during transcription, suggesting that, in addition to its essential role in transcription initiation, it also participates as a regulatory factor.	epigenetic alterations	Homo sapiens	The Transcriptional Complexity of the TFIIH Complex	10.1016/j.tig.2003.08.005	unknown	Unknown	2966
H2AFX	H2AX; H2A.X	H2A histone family, member X	H2AFX has been involved in DNA repair.	genomic instability	Homo sapiens	Genomic Instability in Mice Lacking Histone H2AX	10.1126/science.1069398	unknown	Unknown	3014
HBP1	HMG Box-Containing Protein 1	HMG-box transcription factor 1	HBP1 has been related to DNA unwinding and stress response.	genomic instability	Homo sapiens	HBP1: a HMG box transcriptional repressor that is targeted by the retinoblastoma family	10.1101/gad.11.3.383	unknown	Unknown	26959
HDAC1	HD1; GON-10; RPD3L1	histone deacetylase 1	HDAC1 performs the deacetylation of histones and is an important player in may processes such as development, transcriptional regulation, and cell cycle progression.	epigenetic alterations	Homo sapiens	Histone Deacetylases (HDACs): Characterization of the Classical HDAC Family	10.1042/BJ20021321	hsa04110	Cell cycle	3065
HDAC2	RPD3; YAF1	histone deacetylase 2	HDAC2 performs the deacetylation of histones and is an important player in may processes such as development, transcriptional regulation, and cell cycle progression.	cellular senescence	Homo sapiens	Histone Deacetylases (HDACs): Characterization of the Classical HDAC Family	10.1042/BJ20021321	hsa04110	Cell cycle	3066
HDAC3	SMAP45; HD3	histone deacetylase 3	Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4), and some other non-histone substrates. Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events.	epigenetic alterations	Homo sapiens	Histone deacetylases (HDACs): characterization of the classical HDAC family	10.1042/BJ20021321	unknown	Unknown	8841
HELLS	PASG; SMARCA6; LSH	helicase, lymphoid-specific	The disruption of PASG (lsh), a SNF2-like factor that facilitates DNA methylation, causes global hypomethylation, developmental growth retardation and a premature aging phenotype.	epigenetic alterations	Homo sapiens	Characterization of gene expression, genomic structure, and chromosomal localization of Hells (Lsh)	10.1006/geno.1998.5557	unknown	Unknown	3070
HESX1	RPX; ANF	HESX homeobox 1	HESX1 is an important regulator of development and, particularly, of pituitary development.	others	Homo sapiens	Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse	10.1038/477	hsa04550	Signaling pathways regulating pluripotency of stem cells	8820
HGF	F-TCF; HGFB; HPTA	hepatocyte growth factor	HGF and bFGF derived from hADSCs improved ovarian function during natural aging via reduction of oxidative stress by activating the SIRT1/FOXO1 signaling pathway.	senescence-associated secretory phenotype	Homo sapiens	HGF and BFGF Secretion by Human Adipose-Derived Stem Cells Improves Ovarian Function During Natural Aging via Activation of the SIRT1/FOXO1 Signaling Pathway	10.1159/000487559	hsa04151	PI3K-Akt signaling pathway	3082
HIC1	Zinc Finger And BTB Domain-Containing Protein 29	hypermethylated in cancer 1	Transcriptional repressor. Recognizes and binds to the consensus sequence '5-[CG]NG[CG]GGGCA[CA]CC-3'. May act as a tumor suppressor. May be involved in development of head, face, limbs and ventral body wall. Involved in down-regulation of SIRT1 and thereby is involved in regulation of p53/TP53-dependent apoptotic DNA-damage responses. The specific target gene promoter association seems to be depend on corepressors, such as CTBP1 or CTBP2 and MTA1. The regulation of SIRT1 transcription in response to nutrient deprivation seems to involve CTBP1. Involved in regulation of the Wnt signaling pathway probably by association with TCF7L2 and preventing TCF7L2 and CTNNB1 association with promoters of TCF-responsive genes.	genomic instability	Homo sapiens	Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNA-damage responses	https://doi.org/10.1016/j.cell.2005.08.011	unknown	Unknown	3090
HIF1A	PASD8; MOP1	hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)	Functions as a master transcriptional regulator of the adaptive response to hypoxia.	others	Homo sapiens	Pathobiological Pseudohypoxia as a Putative Mechanism Underlying Myelodysplastic Syndromes	10.1158/2159-8290.CD-17-1203	hsa04066	HIF-1 signaling pathway	3091
HK3	HKIII; HXK3	hexokinase 3	Catalyzes the phosphorylation of hexose, such as D-glucose and D-fructose, to hexose 6-phosphate (D-glucose 6-phosphate and D-fructose 6-phosphate.	others	Homo sapiens	ESR1, HK3 and BRSK1 gene variants are associated with both age at natural menopause and premature ovarian failure	10.1186/1750-1172-7-5	hsa04066	HIF-1 signaling pathway	3101
HMGB1	HMG3; SBP-1; DKFZp686A04236	high mobility group box 1	It is related to DNA unwinding, stress response, and maintenance of genome stability.	genomic instability	Homo sapiens	High Mobility Group Protein B1 Enhances DNA Repair and Chromatin Modification After DNA Damage	10.1073/pnas.0803181105	hsa04140	Autophagy - animal	3146
HMGB2	HMG2	high mobility group box 2	HMGB2 has been related to DNA unwinding and stress response.	genomic instability	Homo sapiens	HMGB2 expression is associated with transition from a quiescent to an activated state of adult neural stem cells	10.1002/dvdy.24559	unknown	Unknown	3148
HOXB7	HOX2; HOX2C	homeobox B7	It is crucial in morphogenesis and development. The expression of many HOX genes, including HOXB7, declines with age, even prior to adulthood.	genomic instability	Homo sapiens	Do Longevity Assurance Genes Containing Hox Domains Regulate Cell Development via Ceramide Synthesis?	10.1016/s0014-5793(02)03248-9	unknown	Unknown	3217
HOXC4	HOX3; HOX3E	homeobox C4	Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.	genomic instability	Homo sapiens	The Binding of Ku Antigen to Homeodomain Proteins Promotes Their Phosphorylation by DNA-dependent Protein Kinase	10.1074/jbc.M100768200	unknown	Unknown	3221
HRAS	P21ras	harvey rat sarcoma viral oncogene homolog	It is involved in the activation of Ras protein signal transduction.	cellular senescence	Homo sapiens	Bladder Cancer and Genetic Mutations	10.1007/s12013-015-0574-z	hsa04211	Longevity regulating pathway	3265
HSF1	HSTF1	heat shock transcription factor 1	It plays a critical role in regulating the transcription of hsp genes. HSF1 in aged rats exhibits a decreased ability to bind DNA.	epigenetic alterations	Homo sapiens	Rethinking HSF1 in Stress, Development, and Organismal Health	10.1016/j.tcb.2017.08.002	unknown	Unknown	3297
HSP90AA1	LAP2	heat shock protein 90kDa alpha (cytosolic), class A member 1	Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction.	others	Homo sapiens	Heat shock response and ageing: mechanisms and applications	10.1006/cbir.2001.0789	hsa04151	PI3K-Akt signaling pathway	3320
HSPA1A	HSP72; HSP70	heat shock 70kDa protein 1A,tissue-specific	Ensuring the correct folding of proteins. Acts as a cellular defense mechanism,the aging-associated variation of the levels of Hsp70 followed a different pattern in post-mitotic and mitotic tissues, being lower or higher in old   comparing to adults, respectively.	loss of proteostasis	Homo sapiens	Hsp70 Basal Levels, a Tissue Marker of the Rate of Aging and Longevity in	10.1016/j.exger.2016.08.013	hsa04010	MAPK signaling pathway	3303
HSPA1B	HSP70-2; HSP72	heat shock 70kDa protein 1B	Stress inducible, ATPase activity, tolerance of hyperthermia,ischemia/hypoxia, resistance to oxidative, UV and TNF stresses,protection against protein aggregation, regulation of HS response,protection of transcription/translation, tumorigenicity,antiapoptotic.	loss of proteostasis	Homo sapiens	Paradoxical Increase of Heat-Shock Response With Age in a Substrain of F344 Rats: Comparison Between F344/DuCrj and F344/Jcl	10.1016/s0047-6374(02)00096-9	hsa04010	MAPK signaling pathway	3304
HSPA8	HSC71; HSC70; HSP73	heat shock 70kDa protein 8	This gene encodes a member of the heat shock protein 70 family, which contains both heat-inducible and constitutively expressed members. This protein belongs to the latter group, which are also referred to as heat-shock cognate proteins. It functions as a chaperone, and binds to nascent polypeptides to facilitate correct folding. It also functions as an ATPase in the disassembly of clathrin-coated vesicles during transport of membrane components through the cell.	loss of proteostasis	Homo sapiens	Heat Shock Response and Ageing: Mechanisms and Applications	10.1006/cbir.2001.0789	hsa04010	MAPK signaling pathway	3312
HSPA9	GRP75; PBP74; HSPA9B	heat shock 70kDa protein 9 (mortalin)	HSPA9 influenced pre-messenger RNA splicing by modulating the inclusion of the exons.	epigenetic alterations	Homo sapiens	Parkinson's Disease-Related Gene Variants Influence pre-mRNA Splicing Processes	10.1016/j.neurobiolaging.2016.07.014	unknown	Unknown	3313
HSPD1	GroEL; HSP60; SPG13	heat shock 60kDa protein 1 (chaperonin)	It is involve in the aging-related apoptotic process, promote aging.	mitochondrial dysfunction	Homo sapiens	Age-related Alterations in Expression of Apoptosis Regulatory Proteins and Heat Shock Proteins in Rat Skeletal Muscle	10.1016/j.bbadis.2005.08.003	unknown	Unknown	3329
HTRA2	Serine Proteinase OMI	HtrA serine peptidase 2	Serine protease that shows proteolytic activity against a non-specific substrate beta-casein. Promotes or induces cell death either by direct binding to and inhibition of BIRC proteins (also called inhibitor of apoptosis proteins, IAPs), leading to an increase in caspase activity, or by a BIRC inhibition-independent, caspase-independent and serine protease activity-dependent mechanism. Cleaves THAP5 and promotes its degradation during apoptosis. Isoform 2 seems to be proteolytically inactive.	loss of proteostasis	Homo sapiens	Characterization of a novel human serine protease that has extensive homology to bacterial heat shock endoprotease HtrA and is regulated by kidney ischemia	10.1074/jbc.275.4.2581	hsa04210	Apoptosis	27429
HTT	IT15; HD	huntingtin	DeltaQ-htt expression in vitro increases autophagosome synthesis and stimulates the Atg5-dependent clearance of truncated N-terminal htt aggregates.	loss of proteostasis	Homo sapiens	Loss of huntingtin-mediated BDNF gene transcription in Huntington's disease	10.1126/science.1059581	unknown	Unknown	3064
IFNB1	Fibroblast Interferon	interferon beta	It has antiviral, antibacterial and anticancer activities.	others	Homo sapiens	Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study	10.2337/dc10-0452	hsa04630	JAK-STAT signaling pathway	3456
IGF1	MGF	insulin-like growth factor 1 (somatomedin C)	The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity.	cellular senescence	Homo sapiens	Insulin-like Growth factor-1 Signaling in Cardiac Aging	10.1016/j.bbadis.2017.08.029	hsa04211	Longevity regulating pathway	3479
IGF1R	CD221; JTK13	insulin-like growth factor 1 receptor	Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity.	others	Homo sapiens	β Cell Aging Markers Have Heterogeneous Distribution and Are Induced by Insulin Resistance	10.1016/j.cmet.2017.03.015	hsa04211	Longevity regulating pathway	3480
IGF2	C11orf43	insulin-like growth factor 2	The insulin-like growth factors possess growth-promoting activity. Major fetal growth hormone in mammals. Plays a key role in regulating fetoplacental development.	cellular senescence	Homo sapiens	Insulin-like growth factors: actions on the skeleton	10.1530/JME-17-0298	hsa04010	MAPK signaling pathway	3481
IGFBP1	AFBP; IBP1; IGF-BP25	insulin like growth factor binding protein 1	As a downstream protein of Jagged1, IGFBP1 was correlated with the severity of coronary atherosclerosis in aging patients, and the increase of circulating IGFBP1 levels with aging may be an adaptive response to counter HCAEC senescence through Akt signaling.	senescence-associated secretory phenotype	Homo sapiens	Role of IGFBP1 in the senescence of vascular endothelial cells and severity of aging?related coronary atherosclerosis	10.3892/ijmm.2019.4338	unknown	Unknown	3484
IGFBP2	IGF-Binding Protein 2	insulin-like growth factor binding protein 2, 36kDa	Inhibits IGF-mediated growth and developmental rates. IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors.	others	Homo sapiens	Duplication of the IGFBP-2 gene in teleost fish: protein structure and functionality conservation and gene expression divergence	10.1371/journal.pone.0003926	unknown	Unknown	3485
IGFBP3	IGFBP-3; BP-53	insulin-like growth factor binding protein 3	IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture.	cellular senescence	Homo sapiens	IGFBP-3 Plays an Important Role in Senescence as an Aging Marker	10.1016/j.etap.2018.03.014	hsa04115	p53 signaling pathway	3486
IKBKB	Inhibitor Of Nuclear Factor Kappa-B Kinase Subunit Beta	inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta	Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation. Phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues.	altered intercellular communication	Homo sapiens	Ro52-mediated monoubiquitination of IKK{beta} down-regulates NF-{kappa}B signalling	10.1093/jb/mvp127	hsa04910	Insulin signaling pathway	3551
IKBKG	IKK-Gamma	Inhibitor Of Nuclear Factor Kappa B Kinase Regulatory Subunit	Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. Its binding to scaffolding polyubiquitin seems to play a role in IKK activation by multiple signaling receptor pathways. However, the specific type of polyubiquitin recognized upon cell stimulation (either 'Lys-63'-linked or linear polyubiquitin) and its functional importance is reported conflictingly. Also considered to be a mediator for TAX activation of NF-kappa-B. Could be implicated in NF-kappa-B-mediated protection from cytokine toxicity. Essential for viral activation of IRF3. Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires 'Lys-27'-linked polyubiquitination.	NF-κB related gene	Homo sapiens	GSK-3β controls NF-kappaB activity via IKKγ/NEMO	10.1038/srep38553	hsa04064	NF-kappa B signaling pathway	8517
IL15	IL-15	interleukin 15	Endurance exercise attenuates age-associated changes to skin in humans and mice and exercise-induced IL-15 is a novel regulator of mitochondrial function in aging skin.	senescence-associated secretory phenotype	Homo sapiens	Exercise-stimulated interleukin-15 is controlled by AMPK and regulates skin metabolism and aging	10.1111/acel.12341	hsa04060	Cytokine-cytokine receptor interaction	3600
IL1A	IL-1A; IL1; IL1F1	interleukin 1 alpha	Reduced IL1A diminished NF-κB transcriptional activity, which controls much of the SASP; exogenous IL1A restored IL6 secretion to rapamycin-treated cells.	senescence-associated secretory phenotype	Homo sapiens	MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation	10.1038/ncb3195	hsa05010	Alzheimer disease	3552
IL1B	IL-1; IL1-BETA; IL1F2	interleukin 1 beta	Aged adipose B cells (AABs) express IL-1R, and inhibition of IL-1 signaling reduces their proliferation and increases lipolysis in aging.	senescence-associated secretory phenotype	Homo sapiens	Aging Induces an Nlrp3 Inflammasome-Dependent Expansion of Adipose B Cells That Impairs Metabolic Homeostasis	10.1016/j.cmet.2019.10.006	hsa04010	MAPK signaling pathway	3553
IL1R1	IL1R; IL1RA; P80	interleukin 1 receptor type 1	IL-1β during the early stages following chronic cerebral hypoperfusion impedes OPC recruitment via IL-1R1, which inhibits white matter repair and functional recovery. IL-1R1 inhibitors may have potential uses in the treatment of SIVD.	NF-κB related gene	Homo sapiens	Interleukin-1β impedes oligodendrocyte progenitor cell recruitment and white matter repair following chronic cerebral hypoperfusion	10.1016/j.bbi.2016.09.024	hsa04064	NF-kappa B signaling pathway	3554
IL2	TCGF	interleukin 2	Produced by T-cells in response to antigenic or mitogenic stimulation, this protein is required for T-cell proliferation and other activities crucial to regulation of the immune response.	cellular senescence	Homo sapiens	Low-affinity TCR Engagement Drives IL-2-dependent Post-Thymic Maintenance of Naive CD4+ T Cells in Aged Humans	10.1111/acel.12353	hsa04630	JAK-STAT signaling pathway	3558
IL2RG	SCIDX1; P64	interleukin 2 receptor, gamma	Common subunit for the receptors for a variety of interleukins.	others	Homo sapiens	Profile of Inflammation-associated genes during Hepatic Differentiation of Human Pluripotent Stem Cells	10.1016/j.dib.2015.10.023	hsa04630	JAK-STAT signaling pathway	3561
IL6	IL-6; BSF2; HGF	interleukin 6	Transgenic mice expressing high levels of IL6 have a reduced growth rate and low levels of IGF1.  IL-6-mediated decrease in IGF-I production represents a major mechanism by which chronic inflammation affects growth.	deregulated nutrient sensing	Homo sapiens	Interleukin 6 Causes Growth Impairment in Transgenic Mice Through a Decrease in Insulin-Like Growth factor-I. A Model for Stunted Growth in Children With Chronic Inflammation	10.1172/JCI119207	hsa04218	Cellular senescence	3569
IL6ST	GP130; HIES4; IL-6RB	interleukin 6 signal transducer	miR-126a-3p also modulates the expression of IRS1, IRS2, IL6ST and PIK3R2, all targets that enforce the hypothesis that senescent endothelial cells may reduce the proliferative ability and the stemness phenotype of bone marrow-derived mesenchymal stem cells.	senescence-associated secretory phenotype	Homo sapiens	The senescent status of endothelial cells affects proliferation, inflammatory profile and SOX2 expression in bone marrow-derived mesenchymal stem cells	10.1016/j.exger.2019.02.014	hsa04630	Cytokine-cytokine receptor interaction	3572
IL7	IL-7	interleukin 7	It stimulates the proliferation of lymphoid progenitors, inhibit aging.	cellular senescence	Homo sapiens	Age-associated Thymic Atrophy Is Linked to a Decline in IL-7 Production	10.1016/s0531-5565(01)00213-3	hsa04630	JAK-STAT signaling pathway	3574
IL7R	CDW127	interleukin 7 receptor	Receptor for interleukin-7. Also acts as a receptor for thymic stromal lymphopoietin (TSLP).	cellular senescence	Homo sapiens	IL7R Gene Expression Network Associates With Human Healthy Ageing	10.1186/s12979-015-0048-6	hsa04630	JAK-STAT signaling pathway	3575
INS	IDDM; ILPR	insulin	Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids.	cellular senescence	Homo sapiens	Brain Insulin Signalling, Glucose Metabolism and Females' Reproductive Aging: A Dangerous Triad in Alzheimer's Disease	10.1016/j.neuropharm.2018.01.044	hsa04211	Longevity regulating pathway	3630
INSR	CD220; HHF5	insulin receptor	Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates.	cellular senescence	Homo sapiens	Cross-species Microarray Analysis With the OSCAR System Suggests an INSR->Pax6->NQO1 Neuro-Protective Pathway in Aging and Alzheimer's DiseaseThe Ubiquitin Ligase CHIP Integrates Proteostasis and Aging by Regulation of Insulin Receptor Turnover	10.1093/nar/gkm408	hsa04211	Longevity regulating pathway	3643
IRS1	HIRS-1	insulin receptor substrate 1	May mediate the control of various cellular processes by insulin.	cellular senescence	Homo sapiens	A novel T608R missense mutation in insulin receptor substrate-1 identified in a subject with type 2 diabetes impairs metabolic insulin signaling	10.1210/jc.2002-020933	hsa04211	Longevity regulating pathway	3667
IRS2	IRS-2	insulin receptor substrate 2	May mediate the control of various cellular processes by insulin.	cellular senescence	Homo sapiens	New amino acid substitutions in the IRS-2 gene in Finnish and Chinese subjects with late-onset type 2 diabetes	10.2337/diabetes.50.8.1949	hsa04211	Longevity regulating pathway	8660
IRS4	Pp160	insulin receptor substrate 4	It acts as an interface between multiple growth factor receptors possessing tyrosine kinase activity, such as insulin receptor, IGF1R and FGFR1, and a complex network of intracellular signaling molecules containing SH2 domains. It is involved in the IGF1R mitogenic signaling pathway. It promotes the AKT1 signaling pathway and BAD phosphorylation during insulin stimulation without activation of RPS6KB1 or the inhibition of apoptosis.	altered intercellular communication	Homo sapiens	Characterization of insulin receptor substrate 4 in human embryonic kidney 293 cells	10.1074/jbc.273.17.10726	hsa04211	Longevity regulating pathway	728340
ITGA2	BR; CD49B; GPIa	integrin subunit alpha 2	Overexpressed ITGA2 promoted the proliferation of ovarian cancer cells. ITGA2 regulated the phosphorylation of forkhead box O1 (FoxO1) by mediating AKT phosphorylation.	senescence-associated secretory phenotype	Homo sapiens	Overexpressed ITGA2 contributes to paclitaxel resistance by ovarian cancer cells through the activation of the AKT/FoxO1 pathway	10.18632/aging.102954	hsa04151	PI3K-Akt signaling pathway	3673
JAK2	JTK10	janus kinase 2	Knockdown or pharmacological inhibition of the JAK-STAT enhances satellite stem cell division potential, resulting in better muscle regeneration. Upon JAK inhibition there was a reduction in inflammatory cytokines and chemokines.	stem cell exhaustion	Homo sapiens	JAK Inhibition Alleviates the Cellular Senescence-Associated Secretory Phenotype and Frailty in Old Age	10.1073/pnas.1515386112	hsa04935	Growth hormone synthesis, secretion and action	3717
JUN	c-Jun; AP-1	jun proto-oncogene	AP-1's DNA-binding activity decreases with age.	genomic instability	Homo sapiens	Increased Constitutive c-Jun N-terminal Kinase Signaling in   Lacking Glutathione S-transferase Pi	10.1074/jbc.M301211200	hsa04310	Wnt signaling pathway	3725
JUND	AP-1	jun D proto-oncogene	His protein has been proposed to protect cells from p53-dependent senescence and apoptosis. Alternative translation initiation site usage results in the production of different isoforms.	cellular senescence	Homo sapiens	Altered composition and DNA binding activity of the AP-1 transcription factor during the ageing of human fibroblasts	10.1016/s0047-6374(01)00319-0	hsa04010	MAPK signaling pathway	3727
KCNA3	Potassium Voltage-Gated Channel; Shaker-Related Subfamily; Member 3	potassium channel, voltage gated shaker related subfamily A, member 3	KCNA3 mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient.	altered intercellular communication	Homo sapiens	Confirmation of the assignment of the gene encoding Kv1.3, a voltage-gated potassium channel (KCNA3) to the proximal short arm of human chromosome 1	10.1006/geno.1994.1500	unknown	Unknown	3738
KCNAB3	KCNA3B; Subunit 3; AKR6A9	potassium voltage-gated channel subfamily A regulatory beta subunit 3	KCNAB3 has potential as a highly informative and specific age biomarker for childhood and adolescence.	others	Homo sapiens	Tracking age-correlated DNA methylation markers in the young	10.1016/j.fsigen.2018.06.011	unknown	Unknown	9196
KL	HFTC3	klotho	KL may have weak glycosidase activity towards glucuronylated steroids.	others	Homo sapiens	The KL-VS Polymorphism of KLOTHO Gene Is Protective Against Retinopathy Incidence in Patients With Type 1 Diabetes	10.1016/j.bbadis.2017.12.015	hsa04211	Longevity regulating pathway	9365
KRAS	C-Ki-Ras	GTPase Kras	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. It plays an important role in the regulation of cell proliferation.It plays a role in promoting oncogenic events by inducing transcriptional silencing of tumor suppressor genes (TSGs) in colorectal cancer (CRC) cells in a ZNF304-dependent manner.	others	Homo sapiens	Regulation of RAS oncogenicity by acetylation.	10.1073/pnas.1201487109	hsa04211	Longevity regulating pathway	8471
LEP	OBS; OB	leptin	LEP is secreted from adipose tissues and is involved in food intake and energy expenditure.	deregulated nutrient sensing	Homo sapiens	Early Onset of Reproductive Function in Normal Female Mice Treated With Leptin	10.1126/science.275.5296.88	hsa04630	JAK-STAT signaling pathway	3952
LEPR	OBR; CD295	leptin receptor	Deletion of LEPR in neurons of mice results in obesity.	deregulated nutrient sensing	Homo sapiens	A Single Nucleotide Polymorphism (SNP) in the Leptin Receptor Is Associated With BMI, Fat Mass and Leptin Levels in Postmenopausal Caucasian Women	10.1007/s004390100468	hsa04630	JAK-STAT signaling pathway	3953
LMNA	CMT2B1; CDCD1	lamin A/C	Lamins are components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane, which is thought to provide a framework for the nuclear envelope and may also interact with chromatin.	genomic instability	Homo sapiens	Differential Stem Cell Aging Kinetics in Hutchinson-Gilford Progeria Syndrome and Werner Syndrome	10.1007/s13238-018-0517-8	hsa04210	Apoptosis	4000
LMNB1	LMN2; ADLD	lamin B1	Lamins are components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane, which is thought to provide a framework for the nuclear envelope and may also interact with chromatin.	cellular senescence	Homo sapiens	The nuclear lamina comes of age	10.1038/nrm1550	hsa04210	Apoptosis	4001
LRP2	gp330; DBS	low density lipoprotein receptor-related protein 2	LRP2 may also help regulate the release of parathyroid hormone.	deregulated nutrient sensing	Homo sapiens	Cloning and Sequencing of Human gp330, a Ca(2+)-binding Receptor With Potential Intracellular Signaling Properties	10.1111/j.1432-1033.1996.0132u.x	unknown	Unknown	4036
MAP3K14	HS; HSNIK; NIK	mitogen-activated protein kinase kinase kinase 14	SNPs in MAP3K14 involved in the NF-κB signalling pathway influence bone mineral density, geometry and turnover in a population-based cohort of middle aged and elderly men.	NF-κB related gene	Homo sapiens	Polymorphisms in genes involved in the NF-κB signalling pathway are associated with bone mineral density, geometry and turnover in men	10.1371/journal.pone.0028031	hsa04064	NF-kappa B signaling pathway	9020
MAP3K5	MAPKKK5; ASK1; MEKK5	mitogen-activated protein kinase kinase kinase 5	It is involved in stress response and apoptosis.	cellular senescence	Homo sapiens	Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways	10.1126/science.275.5296.90	hsa04010	MAPK signaling pathway	4217
MAP3K7	CSCF; FMD2; MEKK7	mitogen-activated protein kinase kinase kinase 7	MAP3K7 is implicated in the cellular response to internal and external environmental changes, playing a crucial role in the inflammation processes that accompany aging.	NF-κB related gene	Homo sapiens	MAP3K7 and GSTZ1 are associated with human longevity: a two-stage case-control study using a multilocus genotyping	10.1007/s11357-012-9416-8	hsa04064	NF-kappa B signaling pathway	6885
MAPK14	PRKM14; p38; Mxi2	mitogen-activated protein kinase 14	It plays an important role in the cascades of cellular responses.	stem cell exhaustion	Homo sapiens	p38MAPK Controls Expression of Multiple Cell Cycle Inhibitors and Islet Proliferation With Advancing Age	10.1016/j.devcel.2009.05.009	hsa04218	Cellular senescence	1432
MAPK3	ERK1; p44mapk; p44erk1	mitogen-activated protein kinase 3	It is?involved in stress response signalling and maybe in cell cycle control.	stem cell exhaustion	Homo sapiens	Influence of Aging and Calorie Restriction on MAPKs Activity in Rat Kidney	10.1016/s0531-5565(02)00082-7	hsa04910	Insulin signaling pathway	5595
MAPK8	JNK; JNK1; SAPK1	mitogen-activated protein kinase 8	MAPK8, also known as JNK1, encodes many transcripts and is an important player in stress response. Overexpression of JNK in roundworms also increases lifespan.	deregulated nutrient sensing	Homo sapiens	JNK Extends Life Span and Limits Growth by Antagonizing Cellular and Organism-Wide Responses to Insulin Signaling	10.1016/j.cell.2005.02.030	hsa04910	Insulin signaling pathway	5599
MAPK9	JNK2; p54a; SAPK	mitogen-activated protein kinase 9	Also called JNK2, MAPK9 encodes many transcripts and is an important player in stress response. Mice without MAPK8 and MAPK9 die at embryonic stages.	stem cell exhaustion	Homo sapiens	JNK Regulates Lifespan in Caenorhabditis Elegans by Modulating Nuclear Translocation of Forkhead Transcription factor/DAF-16	10.1073/pnas.0500749102	hsa04910	Insulin signaling pathway	5601
MAPT	MTBT1; tau; PPND	microtubule-associated protein tau	Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity.	loss of proteostasis	Homo sapiens	Role of Tau Protein in Both Physiological and Pathological Conditions	10.1152/physrev.00024.2003	hsa04010	MAPK signaling pathway	4137
MAX	bHLHd4; bHLHd5; bHLHd6	MYC associated factor X	A transcriptional regulator, MAX can act as pro- or anti-apoptotic.	cellular senescence	Homo sapiens	Role of Mxi1 in Ageing Organ Systems and the Regulation of Normal and Neoplastic Growth	10.1038/31008	hsa04010	MAPK signaling pathway	4149
MDM2	HDM2; MGC5370	MDM2 proto-oncogene, E3 ubiquitin protein ligase	MDM2 is an oncogene that inhibits?TP53. The MDM2 gene encodes multiple transcripts, many of which are tissue-specific. Disruption of MDM2 in mice resulted in increased?TP53-dependent apoptosis and defects in multiple haematopoietic lineages.	cellular senescence	Homo sapiens	mdm2 Is Critical for Inhibition of p53 During Lymphopoiesis and the Response to Ionizing Irradiation	10.1128/mcb.23.2.462-473.2003	hsa04115	p53 signaling pathway	4193
MED1	PBP; TRAP220; RB18A	mediator complex subunit 1	MED1 is involved in embryonic development and important for?SP1?activity.	stem cell exhaustion	Homo sapiens	Roles of PPARs in Health and Disease	10.1038/35013000	unknown	Unknown	5469
MIF	L-Dopachrome Tautomerase	macrophage migration inhibitory factor (glycosylation-inhibiting factor)	Pro-inflammatory cytokine. It is involved in the innate immune response to bacterial pathogens. The expression of MIF at sites of inflammation suggests a role as mediator in regulating the function of macrophages in host defense. It counteracts the anti-inflammatory activity of glucocorticoids. It has phenylpyruvate tautomerase and dopachrome tautomerase activity (in vitro), but the physiological substrate is not known.	others	Homo sapiens	A polymorphism in the macrophage migration inhibitory factor gene is involved in the genetic predisposition of Crohn's disease and associated with cumulative steroid doses	PMID: 17591062	unknown	Unknown	4282
MLH1	DNA Mismatch Repair Protein Mlh1	mutL homolog 1	Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of PMS2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch.	genomic instability	Homo sapiens	Human MutL homolog (MLH1) function in DNA mismatch repair: a prospective screen for missense mutations in the ATPase domain	https://doi.org/10.1093/nar/gkh855	unknown	Unknown	4292
MMP1	CLG; CLGN	matrix metallopeptidase 1	Its expression level in skin fibroblasts was altered in the process of aging, and the cell growth rate was reduced.	senescence-associated secretory phenotype	Homo sapiens	The effect of aging in primary human dermal fibroblasts	10.1371/journal.pone.0219165	hsa04657	IL-17 signaling pathway	4312
MMP10	STMY2	Matrix Metallopeptidase 10	Can degrade fibronectin, gelatins of type I, III, IV, and V; weakly collagens III, IV, and V. Activates procollagenase.	senescence-associated secretory phenotype	Homo sapiens	Exome-wide rare variant analysis in familial essential tremor	10.1016/j.parkreldis.2020.11.021	unknown	Unknown	4319
MMP12	HME	Matrix Metallopeptidase 12	May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3.	senescence-associated secretory phenotype	Homo sapiens	A standardized Terminalia chebula fruit extract alters the expression of genes associated with skin architecture and barrier formation	10.1684/ejd.2020.3882	unknown	Unknown	4321
MMP13	Collagenase 3	Matrix Metallopeptidase 13	Plays a role in the degradation of extracellular matrix proteins including fibrillar collagen, fibronectin, TNC and ACAN. Cleaves triple helical collagens, including type I, type II and type III collagen, but has the highest activity with soluble type II collagen. Can also degrade collagen type IV, type XIV and type X. May also function by activating or degrading key regulatory proteins, such as TGFB1 and CCN2. Plays a role in wound healing, tissue remodeling, cartilage degradation, bone development, bone mineralization and ossification. Required for normal embryonic bone development and ossification. Plays a role in the healing of bone fractures via endochondral ossification. Plays a role in wound healing, probably by a mechanism that involves proteolytic activation of TGFB1 and degradation of CCN2. Plays a role in keratinocyte migration during wound healing. May play a role in cell migration and in tumor cell invasion.	senescence-associated secretory phenotype	Homo sapiens	Cosmeceutical potentials of Curcuma mangga Val. extract in human BJ fibroblasts against MMP1, MMP3, and MMP13	10.1016/j.heliyon.2020.e04921	hsa04657	IL-17 signaling pathway	4322
MMP14	MT1-MMP	Matrix Metallopeptidase 14	Endopeptidase that degrades various components of the extracellular matrix such as collagen. Activates progelatinase A. Essential for pericellular collagenolysis and modeling of skeletal and extraskeletal connective tissues during development (By similarity). May be involved in actin cytoskeleton reorganization by cleaving PTK7 (PubMed:20837484). Acts as a positive regulator of cell growth and migration via activation of MMP15. Involved in the formation of the fibrovascular tissues in association with pro-MMP2 (PubMed:12714657). Cleaves ADGRB1 to release vasculostatin-40 which inhibits angiogenesis.	senescence-associated secretory phenotype	Homo sapiens	Identification of a new pseudogenes/lncRNAs-hsa-miR-26b-5p-COL12A1 competing endogenous RNA network associated with prognosis of pancreatic cancer using bioinformatics analysis	10.18632/aging.103709	hsa04668	TNF signaling pathway	4323
MMP2	TBE-1	Matrix Metallopeptidase 2	Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3beta in vitro. Involved in the formation of the fibrovascular tissues in association with MMP14.	senescence-associated secretory phenotype	Homo sapiens	Galectin-1 promotes vasculogenic mimicry in gastric adenocarcinoma via the Hedgehog/GLI signaling pathway	10.18632/aging.104000	hsa01522	Endocrine resistance	4313
MMP3	Stromelysin-1	Matrix Metallopeptidase 3	Can degrade fibronectin, laminin, gelatins of type I, III, IV, and V; collagens III, IV, X, and IX, and cartilage proteoglycans. Activates procollagenase.	senescence-associated secretory phenotype	Homo sapiens	The effect of aging in primary human dermal fibroblasts	10.1371/journal.pone.0219165	hsa04657	IL-17 signaling pathway	4314
MMP7	Pump-1 Protease	Matrix Metallopeptidase 7	Degrades casein, gelatins of types I, III, IV, and V, and fibronectin. Activates procollagenase.	senescence-associated secretory phenotype	Homo sapiens	Interleukin-17 promotes prostate cancer via MMP7-induced epithelial-to-mesenchymal transition	10.1038/onc.2016.240	hsa04310	Wnt signaling pathway	4316
MSRA	Methionine Sulfoxide Reductase A; PMSR; Peptide Met(O) Reductase	methionine sulfoxide reductase A	A decline in MSRA activity could reduce the antioxidant defenses and increase the oxidation of critical proteins in neurons in the brain in AD.	others	Homo sapiens	Decrease in Peptide Methionine Sulfoxide Reductase in Alzheimer's Disease Brain	10.1046/j.1471-4159.1999.0731660.x	unknown	Unknown	4482
MT-CO1	COX1; COI; MTCO1	mitochondrially encoded cytochrome c oxidase I	MT-CO1 catalyses the reduction of oxygen to water, inactivation of it contributes to """"immortality"""".	mitochondrial dysfunction	Homo sapiens	Mitochondrial Group II Introns, Cytochrome C Oxidase, and Senescence in Podospora Anserina	10.1128/mcb.19.6.4093	unknown	Unknown	4512
MT1E	MT-IE	metallothionein 1E	Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids.	others	Homo sapiens	Induction by zinc of specific metallothionein isoforms in human monocytes	10.1111/j.1432-1033.1994.tb18603.x	unknown	Unknown	4493
MTOR	RAPT1; FLJ44809; FRAP	mechanistic target of rapamycin (serine/threonine kinase)	The MTOR kinase belongs to the target of rapamycin group of enzymes which regulate cellular growth and proliferation. In human cell cultures MTOR inhibition supresses the senescence associated secretory phenotype (SASP), which can disrupt tissues and contribute to age-related pathologies, including cancer.	deregulated nutrient sensing	Homo sapiens	MTOR Regulates the Pro-Tumorigenic Senescence-Associated Secretory Phenotype by Promoting IL1A Translation	10.1038/ncb3195	hsa04211	Longevity regulating pathway	2475
MVK	MK	Mevalonate Kinase	Catalyzes the phosphorylation of mevalonate to mevalonate 5-phosphate, a key step in isoprenoid and cholesterol biosynthesis.	others	Homo sapiens	Allantoin, a Potential Metabolite That Promotes AMPK Phosphorylation and Suppresses Cholesterol Biosynthesis Via the Mevalonate Pathway and Bloch Pathway	10.1007/s12010-020-03265-2	hsa00900	Terpenoid backbone biosynthesis	4598
MXD1	MAD1; bHLHc58; MAD	MAX dimerization protein 1	MXD1 is involved in apoptosis. It forms with?MAX?a transcriptional repressor and might antagonize?MYC?function.	cellular senescence	Homo sapiens	X-ray structures of Myc-Max and Mad-Max recognizing DNA. Molecular bases of regulation by proto-oncogenic transcription factors	10.1016/s0092-8674(02)01284-9	unknown	Unknown	4084
MXI1	MXD2; MAD2; MXI	MAX interactor 1, dimerization protein	Mxi1 is involved in the homeostasis of differentiated organ systems, acts as a tumour suppressor in vivo, and engages the Myc network in a functionally relevant manner.	others	Homo sapiens	Mxi1, a protein that specifically interacts with Max to bind Myc-Max recognition sites	10.1016/0092-8674(93)90662-a	unknown	Unknown	4601
MYC	C-Myc	v-myc avian myelocytomatosis viral oncogene homolog	Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. Activates the transcription of growth-related genes.	cellular senescence	Homo sapiens	Reduced c-Myc signaling triggers telomere-independent senescence by regulating Bmi-1 and p16(INK4a)	10.1073/pnas.0600069103	hsa04218	Cellular senescence	4609
MYD88	MYD88 Innate Immune Signal Transduction Adaptor	Myeloid Differentiation Primary Response 88	Adapter protein involved in the Toll-like receptor and IL-1 receptor signaling pathway in the innate immune response (PubMed:15361868, PubMed:18292575). Acts via IRAK1, IRAK2, IRF7 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:15361868, PubMed:24316379, PubMed:19506249). Increases IL-8 transcription (PubMed:9013863). Involved in IL-18-mediated signaling pathway. Activates IRF1 resulting in its rapid migration into the nucleus to mediate an efficient induction of IFN-beta, NOS2/INOS, and IL12A genes. MyD88-mediated signaling in intestinal epithelial cells is crucial for maintenance of gut homeostasis and controls the expression of the antimicrobial lectin REG3G in the small intestine (By similarity).	others	Homo sapiens	Aging leads to dysfunctional innate immune responses to TLR2 and TLR4 agonists	10.1007/s40520-018-1064-0	hsa04010	MAPK signaling pathway	4615
MYLK	MLCK1	Myosin Light Chain Kinase	Calcium/calmodulin-dependent myosin light chain kinase implicated in smooth muscle contraction via phosphorylation of myosin light chains (MLC). Also regulates actin-myosin interaction through a non-kinase activity. Phosphorylates PTK2B/PYK2 and myosin light-chains. Involved in the inflammatory response (e.g. apoptosis, vascular permeability, leukocyte diapedesis), cell motility and morphology, airway hyperreactivity and other activities relevant to asthma. Required for tonic airway smooth muscle contraction that is necessary for physiological and asthmatic airway resistance. Necessary for gastrointestinal motility.	others	Homo sapiens	Heterozygote genotypes at rs2222823 and rs2811712 SNP loci are associated with cerebral small vessel disease in Han Chinese population	10.1111/j.1755-5949.2012.00322.x	hsa04020	Calcium signaling pathway	4638
NBN	NBS1; P95	nibrin	Component of the MRE11-RAD50-NBN (MRN complex) which plays a critical role in the cellular response to DNA damage and the maintenance of chromosome integrity.	genomic instability	Homo sapiens	Nijmegen Breakage Syndrome Fibroblasts and iPSCs: Cellular Models for Uncovering Disease-Associated Signaling Pathways and Establishing a Screening Platform for Anti-Oxidants	10.1038/s41598-017-07905-2	hsa04218	Cellular senescence	4683
NCOR1	TRAC1	nuclear receptor corepressor 1	NCOR1 mediates transcriptional repression by certain nuclear receptors. It promotes histone deacetylation and the formation of repressive chromatin structures which may impede the access of basal transcription factors.	cellular senescence	Homo sapiens	Exchange of N-CoR corepressor and Tip60 coactivator complexes links gene expression by NF-kappaB and beta-amyloid precursor protein	10.1016/s0092-8674(02)00809-7	unknown	Unknown	9611
NCOR2	Thyroid-, Retinoic-Acid-Receptor-Associated Corepressor	nuclear receptor corepressor 2	It mediates the transcriptional repression activity of some nuclear receptors by promoting chromatin condensation, thus preventing access of the basal transcription. Isoform 1 and isoform 4 have different affinities for different nuclear receptors. It is involved in the regulation BCL6-dependent of the germinal center (GC) reactions, mainly through the control of the GC B-cells proliferation and survival.	others	Homo sapiens	A hybrid mechanism of action for BCL6 in B cells defined by formation of functionally distinct complexes at enhancers and promoters	10.1016/j.celrep.2013.06.016	hsa04330	Notch signaling pathway	9612
NFE2L1	Locus Control Region-Factor 1	nuclear factor, erythroid 2-like 1	NFE2L1 constitutes a precursor of the transcription factor NRF1. It is able to detect various cellular stresses, such as cholesterol excess, oxidative stress or proteasome inhibition. In response to stress, it is released from the endoplasmic reticulum membrane following cleavage by the protease DDI2 and translocates into the nucleus to form the transcription factor NRF1.	deregulated nutrient sensing	Homo sapiens	Proteasomal Degradation Is Transcriptionally Controlled by TCF11 via an ERAD-dependent Feedback Loop	10.1016/j.molcel.2010.09.012	unknown	Unknown	4779
NFE2L2	NF-E2-Related Factor 2	nuclear factor, erythroid 2-like 2	NFE2L2 is a ranscription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase 2 detoxifying enzymes, and promotes their expression, thereby neutralizing reactive electrophiles. In normal conditions, ubiquitinated and degraded in the cytoplasm by the BCR(KEAP1) complex.The NFE2L2/NRF2 pathway is also activated in response to selective autophagy: autophagy promotes interaction between KEAP1 and SQSTM1/p62 and subsequent inactivation of the BCR(KEAP1) complex, leading to NFE2L2/NRF2 nuclear accumulation and expression of cytoprotective genes.	genomic instability	Homo sapiens	p62/SQSTM1 Is a Target Gene for Transcription Factor NRF2 and Creates a Positive Feedback Loop by Inducing Antioxidant Response Element-Driven Gene Transcription	10.1074/jbc.M110.118976	unknown	Unknown	4780
NFKB1	KBF1; p105; NFKB-p50	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1	Chronic, progressive low-grade inflammation induced by knockout of the nfkb1 subunit of the transcription factor NF-κB induces premature ageing.	altered intercellular communication	Homo sapiens	Growing old with nuclear factor-kappaB	10.1379/1466-1268(2002)007<0207:gownfb>2.0.co;2	hsa04211	Longevity regulating pathway	4790
NFKB2	P52; LYT10	nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (p49/p100)	NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis.	others	Homo sapiens	NF-kB2 Induces Senescence Bypass in Melanoma via a Direct Transcriptional Activation of EZH2	10.1038/onc.2015.331	hsa04010	MAPK signaling pathway	4791
NFKBIA	IKBA; MAD-3; IkappaBalpha	nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha	NFKBIA may be involved in inflammation, apoptosis, differentiation, and growth.	deregulated nutrient sensing	Homo sapiens	Integrated genomic approaches identify major pathways and upstream regulators in late onset Alzheimer's disease	10.1038/srep12393	hsa04064	NF-kappa B signaling pathway	4792
NGF	HSAN5	nerve growth factor (beta polypeptide)	Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems.	cellular senescence	Homo sapiens	Innovative Therapy for Alzheimer's Disease-With Focus on Biodelivery of NGF	10.3389/fnins.2019.00038	hsa04010	MAPK signaling pathway	4803
NGFR	TNFRSF16; P75	nerve growth factor receptor	Low affinity receptor which can bind to NGF, BDNF, NTF3, and NTF4. Forms a heterodimeric receptor with SORCS2 that binds the precursor forms of NGF, BDNF and NTF3 with high affinity, and has much lower affinity for mature NGF and BDNF. Plays an important role in differentiation and survival of specific neuronal populations during development.	cellular senescence	Homo sapiens	Validation of a priori candidate Alzheimer's disease SNPs with brain amyloid-beta deposition	10.1038/s41598-019-53604-5	hsa04010	MAPK signaling pathway	4804
NLRP3	AGTAVPRL; AII; AVP	NLR family pyrin domain containing 3	Several AMPK-dependent pathways regulate NLRP3 inflammasome activation during aging, suggesting NLRP3 as a potential pharmacological target in age-related diseases.	deregulated nutrient sensing	Homo sapiens	AMP-Activated Protein Kinase Regulation of the NLRP3 Inflammasome during Aging	10.1016/j.tem.2017.10.009	unknown	Unknown	114548
NOG	SYNS1; SYM1	noggin	NOG may be a factor in bone ageing. Essential for cartilage morphogenesis and joint formation.	stem cell exhaustion	Homo sapiens	Impaired Osteoblastic Differentiation, Reduced Bone Formation, and Severe Osteoporosis in Noggin-Overexpressing Mice	10.1172/JCI15543	hsa04350	TGF-beta signaling pathway	9241
NR3C1	GCRST	nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor)	Receptor for glucocorticoids. Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors.	others	Homo sapiens	Glucocorticoid receptor (NR3C1) gene polymorphisms are associated with age and blood parameters in Polish Caucasian nonagenarians and centenarians	10.1016/j.exger.2018.12.006	unknown	Unknown	2908
NRAS	Transforming Protein N-Ras	GTPase Nras	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.	others	Homo sapiens	Pharmacological targeting of STK19 inhibits oncogenic NRAS-driven melanomagenesis	10.1016/j.cell.2019.01.002	hsa04211	Longevity regulating pathway	4893
NRG1	HRGA; SMDF	neuregulin 1	It is a direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors. It concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors.	cellular senescence	Homo sapiens	Therapeutic efficacy of neuregulin 1-expressing human adipose-derived mesenchymal stem cells for ischemic stroke	10.1371/journal.pone.0222587	unknown	Unknown	3084
NUDT1	8-Oxo-DGTPase	nudix (nucleoside diphosphate linked moiety X)-type motif 1	NUDT1 plays a redundant role in sanitizing oxidized nucleotide pools, such as 8-oxo-dGTP pools. It acts as a sanitizing enzyme for oxidized nucleotide pools, thus suppressing cell dysfunction and death induced by oxidative stress. It is able to hydrolyze also the corresponding ribonucleotides, 2-OH-ATP, 8-oxo-GTP and 8-oxo-ATP.	genomic instability	Homo sapiens	The Oxidized Forms of dATP Are Substrates for the Human MutT Homologue, the hMTH1 Protein	10.1074/jbc.274.26.18201	unknown	Unknown	4521
PAPPA	Placenta-Specific 3	pregnancy-associated plasma protein A, pappalysin 1	PAPPA is a metalloproteinase which specifically cleaves insulin-like growth factor binding protein (IGFBP)-5 at the '163-Ser-|-Lys-164' bond. It shows limited proteolysis toward IGFBP-3.	loss of proteostasis	Homo sapiens	Pregnancy-associated plasma protein-A2 (PAPP-A2), a novel insulin-like growth factor-binding protein-5 proteinase	https://doi.org/10.1210/en.2011-0036	unknown	Unknown	5069
PARP1	ADPRT	poly (ADP-ribose) polymerase 1	PARP1 is poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair.	genomic instability	Homo sapiens	Poly(ADP-ribose) polymerase-1, DNA repair and mammalian longevity	10.1016/s0531-5565(02)00144-4	hsa04064	NF-kappa B signaling pathway	142
PCK1	Phosphoenolpyruvate Carboxykinase; Cytosolic [GTP]	phosphoenolpyruvate carboxykinase 1 (soluble)	PCK1 regulates cataplerosis and anaplerosis, the processes that control the levels of metabolic intermediates in the citric acid cycle. At low glucose levels, it catalyzes the cataplerotic conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle. At high glucose levels, it catalyzes the anaplerotic conversion of phosphoenolpyruvate to oxaloacetate.	others	Homo sapiens	Dynamic acetylation of phosphoenolpyruvate carboxykinase toggles enzyme activity between gluconeogenic and anaplerotic reactions	https://doi.org/10.1016/j.molcel.2018.07.031	hsa04910	Insulin signaling pathway	5105
PCMT1	PIMT; Epididymis Secretory Sperm Binding Protein	protein-L-isoaspartate (D-aspartate) O-methyltransferase	It plays a role in the repair and/or degradation of damaged proteins, promote aging.	loss of proteostasis	Homo sapiens	Improved Rotorod Performance and Hyperactivity in   Deficient in a Protein Repair Methyltransferase	10.1016/j.bbr.2003.11.007	unknown	Unknown	5110
PCNA	Proliferating Cell Nuclear Antigen; Cyclin; ATLD2	proliferating cell nuclear antigen	PCNA is an important player in DNA replication and, probably, in DNA repair, and it interacts with WRN.	genomic instability	Homo sapiens	Hypomorphic PCNA mutation underlies a human DNA repair disorder	10.1172/JCI74593	hsa04110	Cell cycle	5111
PDGFB	PDGF2; SIS	platelet-derived growth factor beta polypeptide	It is a growth factor that plays an essential role in the regulation of embryonic development, cell proliferation, cell migration, survival and chemotaxis.	cellular senescence	Homo sapiens	Platelet-derived Growth Factor B Induces Senescence and Transformation in Normal Human Fibroblasts	10.18632/aging.100577	hsa04010	MAPK signaling pathway	5155
PDGFRA	Platelet-Derived Growth Factor Receptor Alpha	platelet-derived growth factor receptor, alpha polypeptide	Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis. Depending on the context, promotes or inhibits cell proliferation and cell migration. It plays an important role in the differentiation of bone marrow-derived mesenchymal stem cells. It is required for normal skeleton development and cephalic closure during embryonic development. Required for normal development of the mucosa lining the gastrointestinal tract, and for recruitment of mesenchymal cells and normal development of intestinal villi.	altered intercellular communication	Homo sapiens	Independent expression of human alpha or beta platelet-derived growth factor receptor cDNAs in a naive hematopoietic cell leads to functional coupling with mitogenic and chemotactic signaling pathways	10.1073/pnas.86.21.8314	hsa04010	MAPK signaling pathway	5156
PDGFRB	CD140B	platelet-derived growth factor receptor, beta polypeptide	PDGFRB is a tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic development, cell proliferation, survival, differentiation, chemotaxis and migration.	others	Homo sapiens	Premature Aging Syndrome, Penttinen Type: Report of a Chinese Case With a PDGFRB Mutation	10.2340/00015555-2993	hsa04010	MAPK signaling pathway	5159
PDPK1	PDK1	3-phosphoinositide dependent protein kinase 1	PDK1 functions as a master kinase, phosphorylating and activating PKB/Akt, S6K and RSK. PDK1 is essential for embryonic development, and regulates cell size independently of cell number or proliferation, as well as insulin's ability to activate PKB, S6K and RSK.	others	Homo sapiens	PPARβ/δ promotes HRAS-induced senescence and tumor suppression by potentiating p-ERK and repressing p-AKT signaling	10.1038/onc.2013.477	hsa04910	Insulin signaling pathway	5170
PECAM1	CD31 Antigen	Platelet And Endothelial Cell Adhesion Molecule 1	Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (PubMed:19342684, PubMed:17580308). Tyr-690 plays a critical role in TEM and is required for efficient trafficking of PECAM1 to and from the lateral border recycling compartment (LBRC) and is also essential for the LBRC membrane to be targeted around migrating leukocytes (PubMed:19342684). Trans-homophilic interaction may play a role in endothelial cell-cell adhesion via cell junctions (PubMed:27958302). Heterophilic interaction with CD177 plays a role in transendothelial migration of neutrophils (PubMed:17580308). Homophilic ligation of PECAM1 prevents macrophage-mediated phagocytosis of neighboring viable leukocytes by transmitting a detachment signal (PubMed:12110892). Promotes macrophage-mediated phagocytosis of apoptotic leukocytes by tethering them to the phagocytic cells; PECAM1-mediated detachment signal appears to be disabled in apoptotic leukocytes (PubMed:12110892). Modulates bradykinin receptor BDKRB2 activation (PubMed:18672896). Regulates bradykinin- and hyperosmotic shock-induced ERK1/2 activation in endothelial cells (PubMed:18672896). Induces susceptibility to atherosclerosis (By similarity).	senescence-associated secretory phenotype	Homo sapiens	SIRT7 deficiency suppresses inflammation, induces EndoMT, and increases vascular permeability in primary pulmonary endothelial cells	10.1038/s41598-020-69236-z	hsa04514	Cell adhesion molecules	5175
PEX5	Peroxisomal Targeting Signal 1 Receptor	PEX5-related protein	PEX5 is an accessory subunit of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, regulating their cell-surface expression and cyclic nucleotide dependence.	others	Homo sapiens	Peroxisomal targeting signal-1 recognition by the TPR domains of human PEX5	10.1038/81930	unknown	Unknown	5830
PIAS4	PIASY	Protein Inhibitor Of Activated STAT 4	Functions as an E3-type small ubiquitin-like modifier (SUMO) ligase, stabilizing the interaction between UBE2I and the substrate, and as a SUMO-tethering factor. Plays a crucial role as a transcriptional coregulation in various cellular pathways, including the STAT pathway, the p53/TP53 pathway, the Wnt pathway and the steroid hormone signaling pathway. Involved in gene silencing. Mediates sumoylation of CEBPA, PARK7, HERC2, MYB, TCF4 and RNF168. In Wnt signaling, represses LEF1 and enhances TCF4 transcriptional activities through promoting their sumoylations. Enhances the sumoylation of MTA1 and may participate in its paralog-selective sumoylation.	NF-κB related gene	Homo sapiens	Regulation of Stress-Inducible Phosphoprotein 1 Nuclear Retention by Protein Inhibitor of Activated STAT PIAS1	10.1074/mcp.M113.031005	hsa04064	NF-kappa B signaling pathway	51588
PIDD1	LRDD	P53-Induced Death Domain Protein 1	Component of the DNA damage/stress response pathway that functions downstream of p53/TP53 and can either promote cell survival or apoptosis (PubMed:10973264, PubMed:15073321, PubMed:16360037, PubMed:17159900). Associated with CRADD and the CASP2 caspase, it forms the PIDDosome a complex that activates CASP2 and triggers apoptosis (PubMed:15073321, PubMed:17159900). Associated with IKBKG and RIPK1, it enhances sumoylation and ubiquitination of IKBKG which is important for activation of the transcription factor NF-kappa-B (PubMed:16360037, PubMed:17159900).	NF-κB related gene	Homo sapiens	The PIDDosome activates p53 in response to supernumerary centrosomes	10.1101/gad.289728.116	hsa04064	NF-kappa B signaling pathway	55367
PIGF	GPI11 Homolog	Phosphatidylinositol Glycan Anchor Biosynthesis Class F	Involved in GPI-anchor biosynthesis through the transfer of ethanolamine phosphate to the third mannose of GPI.	others	Homo sapiens	Hierarchical Clustering Analyses of Plasma Proteins in Subjects With Cardiovascular Risk Factors Identify Informative Subsets Based on Differential Levels of Angiogenic and Inflammatory Biomarkers	10.3389/fnins.2020.00084	hsa00563	Glycosylphosphatidylinositol (GPI)-anchor biosynthesis	5281
PIK3CA	Serine/Threonine Protein Kinase PIK3CA	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. It participates in cellular signaling in response to various growth factors. It is involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF.	altered intercellular communication	Homo sapiens	Phosphoinositide 3-kinase signaling pathway mediated by p110{alpha} regulates invadopodia formation	10.1083/jcb.201009126	hsa04211	Longevity regulating pathway	5290
PIK3CB	PIK3C1	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta	PIK3CB is a phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology.	cellular senescence	Homo sapiens	Coordinated Expression of Phosphoinositide Metabolic Genes During Development and Aging of Human Dorsolateral Prefrontal Cortex	10.1371/journal.pone.0132675	hsa04211	Longevity regulating pathway	5291
PIK3CD	Phosphoinositide-3-Kinase C	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform	Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Mediates immune responses. It plays a role in B-cell development, proliferation, migration, and function. It is required for B-cell receptor (BCR) signaling.	altered intercellular communication	Homo sapiens	p37delta is a new isoform of PI3K p110delta that increases cell proliferation and is overexpressed in tumors	10.1038/onc.2011.492	hsa04211	Longevity regulating pathway	5293
PIK3R1	GRB1; p85-ALPHA; p85	phosphoinositide-3-kinase, regulatory subunit 1 (alpha)	Together with?PIK3CB, PIK3R1 is involved in insulin (INS) signalling and energy metabolism.	mitochondrial dysfunction	Homo sapiens	CircRNA AFF4 promotes osteoblast cells proliferation and inhibits apoptosis via the Mir-7223-5p/PIK3R1 axis	10.18632/aging.102524	hsa04211	Longevity regulating pathway	5295
PIK3R2	PtdIns-3-Kinase Regulatory Subunit P85-Beta	Phosphatidylinositol 3-kinase regulatory subunit beta	Regulatory subunit of phosphoinositide-3-kinase (PI3K), a kinase that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Binds to activated (phosphorylated) protein-tyrosine kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Indirectly regulates autophagy. Promotes nuclear translocation of XBP1 isoform 2 in a ER stress- and/or insulin-dependent manner during metabolic overloading in the liver and hence plays a role in glucose tolerance improvement.	altered intercellular communication	Homo sapiens	FBXL2- and PTPL1-mediated degradation of p110-free p85beta regulatory subunit controls the PI(3)K signalling cascade	10.1038/ncb2731	hsa04211	Longevity regulating pathway	5296
PIK3R3	PtdIns-3-Kinase Regulatory Subunit P55-Gamma	Phosphatidylinositol 3-kinase regulatory subunit gamma	PIK3R3 binds to activated (phosphorylated) protein-tyrosine kinases through its SH2 domain and regulates their kinase activity. During insulin stimulation, it also binds to IRS-1.	altered intercellular communication	Homo sapiens	Cloning of human p55 gamma, a regulatory subunit of phosphatidylinositol 3-kinase, by a yeast two-hybrid library screen with the insulin-like growth factor-I receptor	10.1016/s0378-1119(98)00045-6	hsa04211	Longevity regulating pathway	8503
PIN1	UBL5; DOD	peptidylprolyl cis/trans isomerase, NIMA-interacting 1	Peptidyl-prolyl cis/trans isomerase (PPIase) binds to and isomerizes specific phosphorylated Ser/Thr-Pro (pSer/Thr-Pro) motifs. By inducing conformational changes in a subset of phosphorylated proteins, it acts as a molecular switch in multiple cellular processes.	cellular senescence	Homo sapiens	The Role of Pin1 Protein in Aging of Human Tendon stem/progenitor Cells	10.1016/j.bbrc.2015.06.163	unknown	Unknown	5300
PLAU	UPA; ATF	plasminogen activator, urokinase	PLAU specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.	others	Homo sapiens	Functional Networks of Aging Markers in the Glomeruli of IgA Nephropathy: A New Therapeutic Opportunity	10.18632/oncotarget.9033	hsa04064	NF-kappa B signaling pathway	5328
PLAUR	UPAR	Plasminogen Activator, Urokinase Receptor	Acts as a receptor for urokinase plasminogen activator. Plays a role in localizing and promoting plasmin formation. Mediates the proteolysis-independent signal transduction activation effects of U-PA. It is subject to negative-feedback regulation by U-PA which cleaves it into an inactive form.	others	Homo sapiens	Urokinase-type plasminogen activator receptor is associated with the development of adipose tissue	10.1160/TH10-02-0101	hsa04610	Complement and coagulation cascades	5329
PLCG1	PLC-Gamma-1	Phospholipase C Gamma 1	Mediates the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Plays an important role in the regulation of intracellular signaling cascades. Becomes activated in response to ligand-mediated activation of receptor-type tyrosine kinases, such as PDGFRA, PDGFRB, FGFR1, FGFR2, FGFR3 and FGFR4. Plays a role in actin reorganization and cell migration.	NF-κB related gene	Homo sapiens	Forebrain-specific ablation of phospholipase Cγ1 causes manic-like behavior	10.1038/mp.2016.261	hsa04064	NF-kappa B signaling pathway	5335
PLCG2	APLAID; FCAS	phospholipase C, gamma 2 (phosphatidylinositol-specific)	The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. It is a crucial enzyme in transmembrane signaling.	others	Homo sapiens	Correction To: A Nonsynonymous Mutation in PLCG2 Reduces the Risk of Alzheimer's Disease, Dementia With Lewy Bodies and Frontotemporal Dementia, and Increases the Likelihood of Longevity	10.1007/s00401-019-02107-8	hsa04935	Growth hormone synthesis, secretion and action	5336
PMCH	Pro-MCH	pro-melanin-concentrating hormone	MCH may act as a neurotransmitter or neuromodulator in a broad array of neuronal functions directed toward the regulation of goal-directed behavior, such as food intake, and general arousal. May also have a role in spermatocyte differentiation.	others	Homo sapiens	Melanin-concentrating hormone functions in the nervous system: food intake and stress	https://doi.org/10.1517/14728222.7.4.495	unknown	Unknown	5367
PML	MYL; TRIM19; RNF71	promyelocytic leukemia	PML also appears to control cell proliferation and cellular senescence. PML IV-induced senescence involves stabilization and activation of p53.	cellular senescence	Homo sapiens	Deconstructing PML-induced Premature Senescence	10.1093/emboj/cdf341	unknown	Unknown	5371
POLA1	p180; POLA; NSX	polymerase (DNA directed), alpha 1, catalytic subunit	POLA1 is involved in DNA replication.	genomic instability	Homo sapiens	Age-related Changes in the Induction of DNA Polymerases in Rat Liver by Gamma-Ray Irradiation	10.1016/s0047-6374(02)00119-7	unknown	Unknown	5422
POLB	DNA Polymerase Beta Subunit; DNA Pol Beta	polymerase (DNA directed), beta	POLB is a repair polymerase that plays a key role in base-excision repair. Has 5'-deoxyribose-5-phosphate lyase (dRP lyase) activity that removes the 5' sugar phosphate and also acts as a DNA polymerase that adds one nucleotide to the 3' end of the arising single-nucleotide gap. Conducts 'gap-filling' DNA synthesis in a stepwise distributive fashion rather than in a processive fashion as for other DNA polymerases.	genomic instability	Homo sapiens	Structure and Mechanism of DNA Polymerase β	10.1021/bi500139h	unknown	Unknown	5423
POLD1	CDC2; POLD	polymerase (DNA directed), delta 1, catalytic subunit	POLD1 is mostly involved in DNA synthesis.	genomic instability	Homo sapiens	Interactions Between the Werner Syndrome Helicase and DNA Polymerase Delta Specifically Facilitate Copying of Tetraplex and Hairpin Structures of the d(CGG)n Trinucleotide Repeat Sequence	10.1074/jbc.M100253200	unknown	Unknown	5424
POLG	MDP1; PEO	polymerase (DNA directed), gamma	POLG is involved in the replication of mitochondrial DNA. It associates with mitochondrial DNA.	mitochondrial dysfunction	Homo sapiens	DNA polymerase gamma in mitochondrial DNA replication and repair	10.1100/tsw.2003.09	unknown	Unknown	5428
PON1	ESA; PON	paraoxonase 1	PON1 hydrolyzes toxic compounds and is associated with neurodegenerative diseases.	others	Homo sapiens	Genetic Polymorphism of Paraoxonase 1 (PON1) and Susceptibility to Parkinson's Disease	10.1016/s0006-8993(98)00586-1	unknown	Unknown	5444
POU1F1	PIT1; GHF1	POU class 1 homeobox 1	POU1F1 is a transcription factor involved in the specification of the lactotrope, somatotrope, and thyrotrope phenotypes in the developing anterior pituitary.	loss of proteostasis	Homo sapiens	PIT1 abnormality	10.1016/s1096-6374(99)80076-8	hsa04935	Growth hormone synthesis, secretion and action	5449
PPARA	NR1C1	peroxisome proliferator-activated receptor alpha	PPARA is a ligand-activated transcription factor and a key regulator of lipid metabolism.	others	Homo sapiens	Roles of PPARs in health and disease	10.1038/35013000	unknown	Unknown	5465
PPARG	Nuclear Receptor Subfamily 1 Group C Member 3	peroxisome proliferator-activated receptor gamma	Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. It is a key regulator of adipocyte differentiation and glucose homeostasis.	deregulated nutrient sensing	Homo sapiens	Mycobacterium tuberculosis 19-kDa lipoprotein induces Toll-like receptor 2-dependent peroxisome proliferator-activated receptor gamma expression and promotes inflammatory responses in human macrophages	10.3892/mmr.2014.3070	hsa04211	Longevity regulating pathway	5468
PPARGC1A	PPARG Coactivator 1 Alpha	peroxisome proliferator-activated receptor gamma, coactivator 1 alpha	Transcriptional coactivator for steroid receptors and nuclear receptors. It greatly increases the transcriptional activity of PPARG and thyroid hormone receptor on the uncoupling protein promoter. It can regulate key mitochondrial genes that contribute to the program of adaptive thermogenesis. It plays an essential role in metabolic reprogramming in response to dietary availability through coordination of the expression of a wide array of genes involved in glucose and fatty acid metabolism.	altered intercellular communication	Homo sapiens	A tissue-specific coactivator of steroid receptors, identified in a functional genetic screen	10.1128/mcb.20.7.2411-2422.2000	hsa04211	Longevity regulating pathway	10891
PPM1D	Protein Phosphatase 1D Magnesium-Dependent; Delta Isoform	protein phosphatase, Mg2+/Mn2+ dependent, 1D	It is required for the relief of p53-dependent checkpoint mediated cell cycle arrest. It binds to and dephosphorylates 'Ser-15' of TP53 and 'Ser-345' of CHEK1 which contributes to the functional inactivation of these proteins. It is also an important regulator of global heterochromatin silencing and critical in maintaining genome integrity.	genomic instability	Homo sapiens	PPM1D Dephosphorylates Chk1 and p53 and Abrogates Cell Cycle Checkpoints	10.1101/gad.1291305	hsa04115	p53 signaling pathway	8493
PPP1CA	PP1A; PP-1A; PP1alpha	protein phosphatase 1, catalytic subunit, alpha isozyme	It is involved in different cellular processes including cell division, protein synthesis, and synaptic plasticity.	loss of proteostasis	Homo sapiens	Protein Phosphatase 1 Is a Molecular Constraint on Learning and Memory	10.1038/nature00928	hsa04910	Insulin signaling pathway	5499
PRDX1	NKEFA; PAGA	peroxiredoxin 1	Prdx1 is an important defence against oxidants in ageing mice. Prdx1-deficient fibroblasts show decreased proliferation and increased sensitivity to oxidative DNA damage.	others	Homo sapiens	PRDX1 and MTH1 cooperate to prevent ROS-mediated inhibition of telomerase	10.1101/gad.313460.118	unknown	Unknown	5052
PRKAA1	AMPK Subunit Alpha-1	5'-AMP-activated protein kinase catalytic subunit alpha-1	Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators.	deregulated nutrient sensing	Homo sapiens	The energy sensor AMP-activated protein kinase directly regulates the mammalian FOXO3 transcription factor	10.1074/jbc.M705325200	hsa04211	Longevity regulating pathway	5562
PRKAA2	AMPK Subunit Alpha-2	5'-AMP-activated protein kinase catalytic subunit alpha-2	Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators.	deregulated nutrient sensing	Homo sapiens	The energy sensor AMP-activated protein kinase directly regulates the mammalian FOXO4 transcription factor	10.1074/jbc.M705325201	hsa04211	Longevity regulating pathway	5563
PRKAB1	AMPK Subunit Beta-1	5'-AMP-activated protein kinase subunit beta-1	Non-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators.	others	Homo sapiens	Non-catalytic beta and gamma subunits isoforms of the AMP-activated protein kinase	10.1074/jbc.271.15.8675	hsa04211	Longevity regulating pathway	5564
PRKAB2	AMPK Subunit Beta-2	5'-AMP-activated protein kinase subunit beta-2	Non-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators.	others	Homo sapiens	Non-catalytic beta and gamma subunits isoforms of the AMP-activated protein kinase	10.1074/jbc.271.15.8676	hsa04211	Longevity regulating pathway	5565
PRKACA	CAMP-Dependent Protein Kinase Catalytic Subunit Alpha	cAMP-dependent protein kinase catalytic subunit alpha	PRKACA phosphorylates a large number of substrates in the cytoplasm and the nucleus. It regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. It is involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP.	others	Homo sapiens	DNA binding of repressor nuclear factor-kappaB p50/p50 depends on phosphorylation of Ser337 by the protein kinase A catalytic subunit	10.1074/jbc.M412180200	hsa04211	Longevity regulating pathway	5566
PRKACB	CAMP-Dependent Protein Kinase Catalytic Subunit Beta	cAMP-dependent protein kinase catalytic subunit beta	PRKACB mediates cAMP-dependent signaling triggered by receptor binding to GPCRs. PKA activation regulates diverse cellular processes such as cell proliferation, the cell cycle, differentiation and regulation of microtubule dynamics, chromatin condensation and decondensation, nuclear envelope disassembly and reassembly, as well as regulation of intracellular transport mechanisms and ion flux. It regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis.	altered intercellular communication	Homo sapiens	c-MYC activates protein kinase A (PKA) by direct transcriptional activation of the PKA catalytic subunit beta (PKA-CB) gene	10.1038/sj.onc.1205986	hsa04211	Longevity regulating pathway	5567
PRKACG	PKA C-Gamma	cAMP-dependent protein kinase catalytic subunit gamma	PRKACG phosphorylates a large number of substrates in the cytoplasm and the nucleus.	others	Homo sapiens	Molecular cloning of a tissue-specific protein kinase (C gamma) from human testis -- representing a third isoform for the catalytic subunit of cAMP-dependent protein kinase	10.1210/mend-4-3-465	hsa04211	Longevity regulating pathway	5568
PRKAG1	AMPK Gamma1	5'-AMP-activated protein kinase subunit gamma-1	AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators.	others	Homo sapiens	AMPK is a direct adenylate charge-regulated protein kinase	10.1126/science.1200094	hsa04211	Longevity regulating pathway	5571
PRKAG2	AMPK Subunit Gamma-2	5'-AMP-activated protein kinase subunit gamma-2	AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators.	others	Homo sapiens	CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations	10.1172/JCI19874	hsa04211	Longevity regulating pathway	51422
PRKAG3	AMPK Gamma3	5'-AMP-activated protein kinase subunit gamma-3	AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators.	others	Homo sapiens	CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations	10.1172/JCI19874	hsa04211	Longevity regulating pathway	53632
PRKCA	PKCA	protein kinase C, alpha	PRKCA is a phorbol ester receptor involved in signal transduction. Gain-of-function mutations in Protein Kinase Cα (PKCα) may promote synaptic defects in Alzheimer's disease.	others	Homo sapiens	PRKCA polymorphism changes the neural basis of episodic remembering in healthy individuals	10.1371/journal.pone.0098018	hsa04150	mTOR signaling pathway	5578
PRKCB	PKCB	Protein Kinase C Beta	Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signaling and endothelial cells proliferation. Plays a key role in B-cell activation by regulating BCR-induced NF-kappa-B activation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser-644' and 'Ser-652'. Phosphorylation induces CARD11/CARMA1 association with lipid rafts and recruitment of the BCL10-MALT1 complex as well as MAP3K7/TAK1, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1.	NF-κB related gene	Homo sapiens	Molecular identification of protein kinase C beta in Alzheimer's disease	10.18632/aging.103994	hsa04064	NF-kappa B signaling pathway	5579
PRKCD	ALPS3	protein kinase C, delta	Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor-initiated cell death, is involved in tumor suppression as well as survival of several cancers, is required for oxygen radical production by NADPH oxidase and acts as positive or negative regulator in platelet functional responses.	cellular senescence	Homo sapiens	Dysregulated Fc Gamma Receptor-Mediated Phagocytosis Pathway in Alzheimer's Disease: Network-Based Gene Expression Analysis	10.1016/j.neurobiolaging.2019.12.001	hsa04140	Autophagy	5580
PRKCQ	PRKCT	Protein Kinase C Theta	Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that mediates non-redundant functions in T-cell receptor (TCR) signaling, including T-cells activation, proliferation, differentiation and survival, by mediating activation of multiple transcription factors such as NF-kappa-B, JUN, NFATC1 and NFATC2. In TCR-CD3/CD28-co-stimulated T-cells, is required for the activation of NF-kappa-B and JUN, which in turn are essential for IL2 production, and participates in the calcium-dependent NFATC1 and NFATC2 transactivation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11 on several serine residues, inducing CARD11 association with lipid rafts and recruitment of the BCL10-MALT1 complex, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1.	NF-κB related gene	Homo sapiens	Differentially expressed autophagy-related genes are potential prognostic and diagnostic biomarkers in clear-cell renal cell carcinoma	10.18632/aging.102368	hsa04064	NF-kappa B signaling pathway	5588
PRKDC	DNPK1; p350; DNAPK	protein kinase, DNA-activated, catalytic polypeptide	DNA-PK phosphorylates threonines 5 and 7 of HSP90α, decreasing its chaperone function for clients such as AMP-activated protein kinase (AMPK), which is critical for mitochondrial biogenesis and energy metabolism.	mitochondrial dysfunction	Homo sapiens	DNA-PK Promotes the Mitochondrial, Metabolic, and Physical Decline That Occurs During Aging	10.1016/j.cmet.2017.04.008	hsa04110	Cell cycle	5591
PROP1	CPHD2	PROP paired-like homeobox 1	PROP1 is possibly involved in the ontogenesis of pituitary gonadotropes, as well as somatotropes, lactotropes and caudomedial thyrotropes.	others	Homo sapiens	Insulin/IGF-1 and ROS signaling pathway cross-talk in aging and longevity determination	10.1016/j.mce.2008.11.025	unknown	Unknown	5626
PSEN1	FAD; S182; PS1	presenilin 1	The PSEN1 gene has multiple transcriptional variants and its functions could include the cleavage of?APP?and notch receptor protein.	cellular senescence	Homo sapiens	APP Processing and Synaptic Plasticity in presenilin-1 Conditional Knockout Mice	10.1016/s0896-6273(01)00417-2	hsa04310	Wnt signaling pathway	5663
PTEN	MMAC1	phosphatase and tensin homolog	Tumor suppressor. Acts as a dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins.	cellular senescence	Homo sapiens	PTEN, Longevity and Age-Related Diseases	10.3390/biomedicines1010017	hsa04115	p53 signaling pathway	5728
PTGES	PIG12	Prostaglandin E Synthase	Terminal enzyme of the cyclooxygenase (COX)-2-mediated prostaglandin E2 (PGE2) biosynthetic pathway. Catalyzes the glutathione-dependent oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2) in response to inflammatory stimuli (PubMed:18682561, PubMed:10377395, PubMed:12672824, PubMed:12460774, PubMed:10869354, PubMed:12244105). Plays a key role in inflammation response, fever and pain (By similarity). Catalyzes also the oxidoreduction of endocannabinoids into prostaglandin glycerol esters and PGG2 into 15-hydroperoxy-PGE2 (PubMed:12244105, PubMed:12672824). In addition, displays low glutathione transferase and glutathione-dependent peroxidase activities, toward 1-chloro-2,4-dinitrobenzene and 5-hydroperoxyicosatetraenoic acid (5-HPETE), respectively (PubMed:12672824).	senescence-associated secretory phenotype	Homo sapiens	Radiation promotes colorectal cancer initiation and progression by inducing senescence-associated inflammatory responses	10.1038/onc.2015.395	hsa01100	Metabolic pathways	9536
PTGS2	COX2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, phenotypic changes, resistance to apoptosis and tumor angiogenesis.	altered intercellular communication	Homo sapiens	Ceramide-induced and Age-Associated Increase in Macrophage COX-2 Expression Is Mediated Through Up-Regulation of NF-kappa B Activity	10.1074/jbc.M207470200	hsa04370	VEGF signaling pathway	5743
PTK2	STK2; FAK; FADK 1	protein tyrosine kinase 2	PTK2 is necessary for fitness, egulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton.	altered intercellular communication	Homo sapiens	PTK2 rs7460 and rs7843014 Polymorphisms and Exceptional Longevity: A Functional Replication Study	10.1089/rej.2014.1570	hsa04935	Growth hormone synthesis, secretion and action	5747
PTK2B	CAKB; PYK2; RAFTK	protein tyrosine kinase 2 beta	Involved in stress response and signal transduction, PTK2B is an important player in a variety of processes including the regulation of ion channels by calcium and MAPK signalling.	cellular senescence	Homo sapiens	Role of Src-specific Phosphorylation Site on Focal Adhesion Kinase for Senescence-Associated Apoptosis Resistance	10.1007/s10495-006-3978-9	hsa04912	GnRH signaling pathway	2185
PTPN1	PTP1B	protein tyrosine phosphatase, non-receptor type 1	PTPN1 is a tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response.	loss of proteostasis	Homo sapiens	miR-125a-5p inhibits tumorigenesis in hepatocellular carcinoma	10.18632/aging.102276	hsa04910	Insulin signaling pathway	5770
PTPN11	PTP2C; SHP2	protein tyrosine phosphatase, non-receptor type 11	PTPN11 acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus.	others	Homo sapiens	PTPN11 mutations are associated with mild growth hormone resistance in individuals with Noonan syndrome	10.1210/jc.2005-0995	hsa04630	JAK-STAT signaling pathway	5781
PYCR1	P5C Reductase 1	pyrroline-5-carboxylate reductase 1	PYCR1 is a housekeeping enzyme that catalyzes the last step in proline biosynthesis. PYCR1 can utilize both NAD and NADP, but has higher affinity for NAD. PYCR1 is involved in the cellular response to oxidative stress.	others	Homo sapiens	Mutations in PYCR1 cause cutis laxa with progeroid features	10.1038/ng.413	unknown	Unknown	5831
RACK1	GNB2L1; Gnb2-rs1; H12.3	receptor for activated C kinase 1	The Receptor for Activated C Kinase 1 (RACK1) is a scaffold protein for different kinases and membrane receptors. It is a key mediator of various pathways and is involved in various biological events including development, immune response, brain activity and cancer.	others	Homo sapiens	Transcriptional regulation of RACK1 and modulation of its expression: Role of steroid hormones and significance in health and aging	10.1016/j.cellsig.2017.02.010	unknown	Unknown	10399
RAD27	ERC11; FEN1; RTH1	multifunctional nuclease RAD27	Its deletion led to significant changes of chronological lifespan in yeast, featuring both lifespan shortening and lifespan extension.	genomic instability	Homo sapiens	Identification of evolutionarily conserved genetic regulators of cellular aging	10.1111/j.1474-9726.2010.00637.x	unknown	Unknown	853747
RAD51	HsRad51; HsT16930; BRCC5; FANCR; RAD51A; RECA	RAD51 recombinase	RAD51 is involved in DNA unwinding and repair.	genomic instability	Homo sapiens	Insights Into DNA Recombination From the Structure of a RAD51-BRCA2 Complex	10.1038/nature01230	unknown	Unknown	5888
RAD52	DNA Repair Protein RAD52 Homolog; Recombination Protein RAD52; RAD52 Homolog, DNA Repair Protein	RAD52 homolog, DNA repair protein	Coordinated WRN and RAD52 activities are involved in replication fork rescue after DNA damage.	genomic instability	Homo sapiens	WRN Interacts Physically and Functionally With the Recombination Mediator Protein RAD52	10.1074/jbc.M303885200	unknown	Unknown	5893
RAE1	Rae1 Protein Homolog; MRNA Export Factor	ribonucleic acid export 1	RAE1 plays a role in mitotic bipolar spindle formation. Binds mRNA. RAE1 may function in nucleocytoplasmic transport and in directly or indirectly attaching cytoplasmic mRNPs to the cytoskeleton.	others	Homo sapiens	Rae1 Interaction With NuMA Is Required for Bipolar Spindle Formation	10.1073/pnas.0609582104	unknown	Unknown	8480
RB1	RB; PPP1R130; OSRC	retinoblastoma 1	Rb is essential for normal mouse development.	others	Homo sapiens	Cellular senescence and tumor suppressor gene p16	10.1002/ijc.27316	hsa04218	Cellular senescence	5925
RB1CC1	RB1-Inducible Coiled-Coil Protein 1	RB1-inducible coiled-coil protein 1	RB1CC1 is involved in autophagy. RB1CC1 regulates early events but also late events of autophagosome formation through direct interaction with Atg16L1. RB1CC1 is involved in repair of DNA damage caused by ionizing radiation, which subsequently improves cell survival by decreasing apoptosis.	others	Homo sapiens	Suppression of Pyk2 kinase and cellular activities by FIP200	10.1083/jcb.149.2.423	hsa04211	Longevity regulating pathway	9821
RECQL4	RecQ4	RecQ helicase-like 4	RECQL4 belongs to RECQ DNA helicase family which has been shown to participate in many aspects of DNA metabolism.  RECQL4 participates in multiple DNA pathways.	genomic instability	Homo sapiens	Aging in Rothmund-Thomson Syndrome and Related RECQL4 Genetic Disorders	10.1016/j.arr.2016.06.002	unknown	Unknown	9401
RELA	p65; NFKB3	v-rel avian reticuloendotheliosis viral oncogene homolog A	NF-kappa B, which consists of two polypeptides, p50 (M(r) 50K) and p65/RelA (M(r) 65K), is thought to be a key regulator of genes involved in responses to infection, inflammation and stress. RelA controls inducible, but not basal, transcription in NF-kappa B-regulated pathways.	altered intercellular communication	Homo sapiens	Growing old with nuclear factor-kappaB	10.1379/1466-1268(2002)007<0207:gownfb>2.0.co;2	hsa04211	Longevity regulating pathway	5970
RELB	V-Rel Avian Reticuloendotheliosis Viral Oncogene Homolog B	RELB Proto-Oncogene, NF-KB Subunit	NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively.	NF-κB related gene	Homo sapiens	Nuclear Factor-κB Dysregulation and α-Synuclein Pathology: Critical Interplay in the Pathogenesis of Parkinson's Disease	10.3389/fnagi.2020.00068	hsa04064	NF-kappa B signaling pathway	5971
RET	CDHF12	Ret Proto-Oncogene	Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell derived neurotrophic factor family ligands. Phosphorylates PTK2/FAK1. Regulates both cell death/survival balance and positional information. Required for the molecular mechanisms orchestration during intestine organogenesis; involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue. Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner. Involved in the development of the neural crest. Active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage. Acts as a dependence receptor; in the presence of the ligand GDNF in somatotrophs (within pituitary), promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF. Regulates nociceptor survival and size. Triggers the differentiation of rapidly adapting (RA) mechanoreceptors. Mediator of several diseases such as neuroendocrine cancers; these diseases are characterized by aberrant integrins-regulated cell migration. Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which induces inhibition of food-intake. Activates MAPK- and AKT-signaling pathways . Isoform 1 in complex with GFRAL induces higher activation of MAPK-signaling pathway than isoform 2 in complex with GFRAL.	others	Homo sapiens	Associations between Plasma Branched Chain Amino Acids and Health Biomarkers in Response to Resistance Exercise Training Across Age	0.3390/nu12103029	hsa05200	Pathways in cancer	5979
RFC4	A1 37 KDa Subunit	Replication factor C subunit 4	The elongation of primed DNA templates by DNA polymerase delta and epsilon requires the action of the accessory proteins proliferating cell nuclear antigen (PCNA) and activator 1. This subunit may be involved in the elongation of the multiprimed DNA template.	genomic instability	Homo sapiens	Studies of the cloned 37-kDa subunit of activator 1 (replication factor C) of HeLa cells	10.1073/pnas.89.12.5211	unknown	Unknown	5984
RGN	SMP30; RC	regucalcin	Senescence marker RGN is a calcium binding protein also called regucalcin. Its expression levels decline with age, and RGN has been linked to age-related changes in calcium signalling in the liver of rats.	others	Homo sapiens	The Emerging Role of Regucalcin as a Tumor Suppressor: Facts and Views	10.2174/1566524016666160714124550	unknown	Unknown	9104
RHEB	GTP-Binding Protein Rheb	GTP-binding protein Rheb	RHEB activates the protein kinase activity of mTORC1, and thereby plays a role in the regulation of apoptosis. RHEB stimulates the phosphorylation of S6K1 and EIF4EBP1 through activation of mTORC1 signaling. RHEB has low intrinsic GTPase activity.	others	Homo sapiens	Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling	10.1073/pnas.202476899	hsa04211	Longevity regulating pathway	6009
RICTOR	Rapamycin-Insensitive Companion Of MTOR	RPTOR independent companion of MTOR, complex 2	Subunit of mTORC2, which regulates cell growth and survival in response to hormonal signals. mTORC2 is activated by growth factors, but, in contrast to mTORC1, seems to be nutrient-insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors.	deregulated nutrient sensing	Homo sapiens	mTORC1-activated S6K1 phosphorylates Rictor on threonine 1135 and regulates mTORC2 signaling	10.1128/MCB.00601-09	hsa04150	mTOR signaling pathway	253260
RIPK1	Cell Death Protein RIP	Receptor Interacting Serine/Threonine Kinase 1	Serine-threonine kinase which is a key regulator of TNF-mediated apoptosis, necroptosis and inflammatory pathways (PubMed:25459879, PubMed:31827281, PubMed:31827280). Exhibits kinase activity-dependent functions that trigger cell death and kinase-independent scaffold functions regulating inflammatory signaling and cell survival (PubMed:11101870, PubMed:25459879). Initiates ripoptocide which describes cell death that is dependent on RIPK1, be it apoptosis or necroptosis (PubMed:31457011). Upon binding of TNF to TNFR1, RIPK1 is recruited to the TNF-R1 signaling complex (TNF-RSC also known as complex I) where it acts as a scaffold protein promoting cell survival, in part, by activating the canonical NF-kB pathway.	NF-κB related gene	Homo sapiens	TBK1 Suppresses RIPK1-Driven Apoptosis and Inflammation during Development and in Aging	10.1016/j.cell.2018.07.041	hsa04064	NF-kappa B signaling pathway	8737
RORA	NR1F1	RAR Related Orphan Receptor A	Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Key regulator of embryonic development, cellular differentiation, immunity, circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism. Considered to have intrinsic transcriptional activity, have some natural ligands like oxysterols that act as agonists (25-hydroxycholesterol) or inverse agonists (7-oxygenated sterols), enhancing or repressing the transcriptional activity, respectively.	others	Homo sapiens	Circadian clock associates with tumor microenvironment in thoracic cancers	10.18632/aging.102450	hsa04710	Circadian rhythm	6095
RPA1	HSSB	replication protein A1, 70kDa	As part of the heterotrimeric replication protein A complex (RPA/RP-A), RPA1 binds and stabilizes single-stranded DNA intermediates, that form during DNA replication or upon DNA stress.	others	Homo sapiens	RNA-Seq Analysis of Differentially Expressed Genes Relevant to Mismatch Repair in Aging Hematopoietic Stem-Progenitor Cells	0.1002/jcb.28417	unknown	Unknown	6117
RPS6KA5	S6K-Alpha-5	Ribosomal Protein S6 Kinase A5	Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factors RELA, STAT3 and ETV1/ER81, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes (PubMed:11909979, PubMed:12569367, PubMed:12763138, PubMed:9687510, PubMed:18511904, PubMed:9873047). Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin.	senescence-associated secretory phenotype	Homo sapiens	A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape	10.1038/ncomms13357	hsa04010	MAPK signaling pathway	9252
RPS6KB1	Ribosomal Protein S6 Kinase Beta-1	ribosomal protein S6 kinase beta-1	Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression. It regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD. It also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling. It mediates cell survival by phosphorylating the pro-apoptotic protein BAD and suppressing its pro-apoptotic function.	others	Homo sapiens	Regulation of elongation factor 2 kinase by p90(RSK1) and p70 S6 kinase	10.1093/emboj/20.16.4370	hsa04211	Longevity regulating pathway	6198
RPS6KB2	S6 Kinase-Related Kinase	ribosomal protein S6 kinase beta-2	It phosphorylates specifically ribosomal protein S6. It seems to act downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression in an alternative pathway regulated by MEAK7.	others	Homo sapiens	Mammalian EAK-7 activates alternative mTOR signaling to regulate cell proliferation and migration	10.1126/sciadv.aao5838	hsa04211	Longevity regulating pathway	6199
RPTOR	P150 Target Of Rapamycin (TOR)-Scaffold Protein Containing WD-Repeats	regulatory-associated protein of mTOR	It involved in the control of the mammalian target of rapamycin complex 1 (mTORC1) activity which regulates cell growth and survival, and autophagy in response to nutrient and hormonal signals; functions as a scaffold for recruiting mTORC1 substrates. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1.	deregulated nutrient sensing	Homo sapiens	mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the growth machinery	10.1016/s0092-8674(02)00808-5	hsa04211	Longevity regulating pathway	57521
S100B	S100; NEF	S100 calcium binding protein B	It weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites.	others	Homo sapiens	Zinc Binding to S100B Affords Regulation of Trace Metal Homeostasis and Excitotoxicity in the Brain	10.3389/fnmol.2017.00456	unknown	Unknown	6285
SDHC	CYB560; PGL3	succinate dehydrogenase complex, subunit C, integral membrane protein, 15kDa	A member of the mitochondrial electron transport chain, SDHC homologues have been implicated in ageing of lower life forms. Mutations in the human SDHC gene have been associated with mitochondrial respiratory chain deficiency.	mitochondrial dysfunction	Homo sapiens	Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency	10.1038/ng1095-144	hsa05010	Alzheimer disease	6391
SERPINB2	Serpin Family B Member 2	Monocyte Arg-Serpin	Inhibits urokinase-type plasminogen activator. The monocyte derived PAI-2 is distinct from the endothelial cell-derived PAI-1.	senescence-associated secretory phenotype	Homo sapiens	An Endogenous Anti-aging Factor, Sonic Hedgehog, Suppresses Endometrial Stem Cell Aging through SERPINB2	10.1016/j.ymthe.2019.04.019	hsa04610	Complement and coagulation cascades	5055
SERPINE1	Endothelial Plasminogen Activator Inhibitor	serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1	Serine protease inhibitor. SERPINE1 inhibits TMPRSS7. It is a primary inhibitor of tissue-type plasminogen activator (PLAT) and urokinase-type plasminogen activator (PLAU). As PLAT inhibitor, it is required for fibrinolysis down-regulation and is responsible for the controlled degradation of blood clots. As PLAU inhibitor, it is involved in the regulation of cell adhesion and spreading.	cellular senescence	Homo sapiens	Plasminogen Activator inhibitor-1 Is a Critical Downstream Target of p53 in the Induction of Replicative Senescence	10.1038/ncb1448	hsa04115	p53 signaling pathway	5054
SESN1	P53 Regulated PA26 Nuclear Protein	Sestrin-1	SESN1 functions as an intracellular leucine sensor that negatively regulates the TORC1 signaling pathway through the GATOR complex. In absence of leucine, SESN1 binds the GATOR subcomplex GATOR2 and prevents TORC1 signaling. Binding of leucine to SESN2 disrupts its interaction with GATOR2 thereby activating the TORC1 signaling pathway. This stress-inducible metabolic regulator may also play a role in protection against oxidative and genotoxic stresses.	others	Homo sapiens	Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD	10.1126/science.1095569	hsa04211	Longevity regulating pathway	27244
SESN2	SEST2	Sestrin-2	SESN2 functions as an intracellular leucine sensor that negatively regulates the TORC1 signaling pathway through the GATOR complex. In absence of leucine, SESN2 binds the GATOR subcomplex GATOR2 and prevents TORC1 signaling. This stress-inducible metabolic regulator also plays a role in protection against oxidative and genotoxic stresses. SESN2 may negatively regulate protein translation in response to endoplasmic reticulum stress, via TORC1.	others	Homo sapiens	Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD	10.1126/science.1095569	hsa04211	Longevity regulating pathway	83667
SESN3	SEST3	Sestrin-3	SESN3 may function as an intracellular leucine sensor that negatively regulates the TORC1 signaling pathway. SESN3 may also regulate the insulin-receptor signaling pathway through activation of TORC2. This metabolic regulator may also play a role in protection against oxidative and genotoxic stresses.	altered intercellular communication	Homo sapiens	The Sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of mTORC1	10.1016/j.celrep.2014.09.014	hsa04211	Longevity regulating pathway	143686
SHC1	SHCA; SHC	SHC (Src homology 2 domain containing) transforming protein 1	Signaling adapter that couples activated growth factor receptors to signaling pathways. SHC1 participates in a signaling cascade initiated by activated KIT and KITLG/SCF.	others	Homo sapiens	Association Analysis of the SHC1 Gene Locus With Longevity in the Japanese Population	10.1007/s00109-003-0485-0	hsa04910	Insulin signaling pathway	6464
SIN3A	KIAA0700; DKFZP434K2235	SIN3 transcription regulator family member A	The protein encoded by this gene is a transcriptional regulatory protein. It contains paired amphipathic helix (PAH) domains, which are important for protein-protein interactions and may mediate repression by the Mad-Max complex.	cellular senescence	Homo sapiens	Expression of Transcriptional Repressor Protein mSin3A but Not mSin3B Is Induced During Neuronal Apoptosis	10.1006/bbrc.1998.9629	unknown	Unknown	25942
SIRT1	SIR2L1	sirtuin 1	SIRT1 is a NAD-dependent deacetylase, which can regulate a number of processes by deacetylating key proteins, such as TP53.	epigenetic alterations	Homo sapiens	Identification of serum sirtuins as novel noninvasive protein markers for frailty	10.1111/acel.12260	hsa04211	Longevity regulating pathway	23411
SIRT2	Sirtuin 2	Silent Mating Type Information Regulation 2 Homolog	This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA.	others	Homo sapiens	The human Sir2 ortholog SIRT2 is an NAD+-dependent tubulin deacetylase	10.1016/s1097-2765(03)00038-8	unknown	Unknown	22933
SIRT3	NAD-Dependent Protein Deacetylase Sirtuin-3	sirtuin 3	NAD-dependent protein deacetylase. SIRT3 activates or deactivates mitochondrial target proteins by deacetylating key lysine residues. SIRT3 contributes to the regulation of the cellular energy metabolism. SIRT3 is important for regulating tissue-specific ATP levels.	mitochondrial dysfunction	Homo sapiens	The human silent information regulator (Sir)2 homologue hSIRT3 is a mitochondrial nicotinamide adenine dinucleotide-dependent deacetylase	https://doi.org/10.1083/jcb.200205057	unknown	Unknown	23410
SIRT6	NAD-Dependent Protein Deacetylase Sirtuin-6; SIR2-Like Protein 6	sirtuin 6	NAD-dependent protein deacetylase. SIRT6 has deacetylase activity towards histone H3K9Ac and H3K56Ac. SIRT6 modulates acetylation of histone H3 in telomeric chromatin during the S-phase of the cell cycle. SIRT6 acts as a corepressor of the transcription factor HIF1A to control the expression of multiple glycolytic genes to regulate glucose homeostasis.	epigenetic alterations	Homo sapiens	Structure and Biochemical Functions of SIRT6	10.1074/jbc.M111.218990	unknown	Unknown	51548
SIRT7	Regulatory Protein SIR2 Homolog 7	sirtuin 7	NAD-dependent protein-lysine deacylase that can act both as a deacetylase or deacylase (desuccinylase, depropionylase and deglutarylase), depending on the context. It specifically mediates deacetylation of histone H3 at 'Lys-18' (H3K18Ac). In contrast to other histone deacetylases, it displays strong preference for a specific histone mark, H3K18Ac, directly linked to control of gene expression. H3K18Ac is mainly present around the transcription start site of genes and has been linked to activation of nuclear hormone receptors; SIRT7 thereby acts as a transcription represso.	epigenetic alterations	Homo sapiens	SIRT7 Links H3K18 Deacetylation to Maintenance of Oncogenic Transformation	10.1038/nature11043	unknown	Unknown	51547
SLC13A1	Renal Sodium/Sulfate Cotransporter	solute carrier family 13 (sodium/sulfate symporter), member 1	Sodium/sulfate cotransporter that mediates sulfate reabsorption in the kidney.	others	Homo sapiens	The human renal sodium sulfate cotransporter (SLC13A1; hNaSi-1) cDNA and gene: organization, chromosomal localization, and functional characterization	10.1006/geno.2000.6404	unknown	Unknown	6561
SNCG	BCSG1; SR; persyn	synuclein, gamma (breast cancer-specific protein 1)	SNCG intracellularly associates with BubR1 together suggest that SNCG expression compromises the mitotic checkpoint control by inhibition of the normal function of BubR1, thereby promoting genetic instability.	genomic instability	Homo sapiens	Synuclein Gamma Inhibits the Mitotic Checkpoint Function and Promotes Chromosomal Instability of Breast Cancer Cells	10.1007/s10549-005-6938-0	unknown	Unknown	6623
SOCS2	Cytokine-Inducible SH2 Protein 2	suppressor of cytokine signaling 2	SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS2 appears to be a negative regulator in the growth hormone/IGF1 signaling pathway. Probable substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.	altered intercellular communication	Homo sapiens	Interaction of human suppressor of cytokine signaling (SOCS)-2 with the insulin-like growth factor-I receptor	10.1006/geno.2000.6404	hsa04910	Insulin signaling pathway	8835
SOD1	IPOA; ALS; ALS1	superoxide dismutase 1, soluble	In a more recent study the kidneys of SOD1-null mice exhibited increased DNA damage, increased senescent cells, and increased inflammation. Subjecting these mice to dietary restriction attenuated these effects.	cellular senescence	Homo sapiens	Amyotrophic lateral sclerosis: a proposed mechanism	10.1073/pnas.132260399	unknown	Unknown	6647
SOD2	Superoxide Dismutase 2; Mn-SOD; MNSOD	superoxide dismutase 2, mitochondrial	Overexpression of SOD2 in aging mouse hearts demonstrated a protective role against oxidative stress, fibrosis and apoptosis.	others	Homo sapiens	The polymorphism of manganese superoxide dismutase is associated with diabetic nephropathy in Japanese type 2 diabetic patients	10.1007/s100380300021	hsa04211	Longevity regulating pathway	6648
SP1	TSFP1	Sp1 transcription factor	SP1 regulates ageing-related genes such as?WRN or cellular senescence-related genes like?CDKN2A.	genomic instability	Homo sapiens	Sp1 Is Essential for p16 Expression in Homo sapiens Diploid Fibroblasts During Senescence	10.1371/journal.pone.0000164	hsa04350	TGF-beta signaling pathway	6667
SPRTN	DNA Damage-Targeting VCP (P97) Adaptor	SprT-like N-terminal domain	SPRTN is recruited to sites of UV damage and interacts with ubiquitinated PCNA and RAD18, the E3 ubiquitin ligase that monoubiquitinates PCNA. SPRTN facilitates chromatin association of RAD18 and is required for efficient PCNA monoubiquitination, promoting a feed-forward loop to enhance PCNA ubiquitination and translesion DNA synthesis. SPRTN acts as a regulator of TLS by recruiting VCP/p97 to sites of DNA damage, possibly leading to extraction of DNA polymerase eta (POLH) by VCP/p97 to prevent excessive translesion DNA synthesis and limit the incidence of mutations induced by DNA damage.	genomic instability	Homo sapiens	DNA-protein crosslink repair: proteases as DNA repair enzymes	10.1016/j.tibs.2014.10.012	unknown	Unknown	83932
SQSTM1	Autophagy Receptor P62	sequestosome 1	Autophagy receptor required for selective macroautophagy (aggrephagy). SQSTM1 functions as a bridge between polyubiquitinated cargo and autophagosomes. SQSTM1 interacts directly with both the cargo to become degraded and an autophagy modifier of the MAP1 LC3 family. Along with WDFY3, SQSTM1 is involved in the formation and autophagic degradation of cytoplasmic ubiquitin-containing inclusions (p62 bodies, ALIS/aggresome-like induced structures).	deregulated nutrient sensing	Homo sapiens	Sequestosome 1/p62 is a polyubiquitin chain binding protein involved in ubiquitin proteasome degradation	10.1128/MCB.24.18.8055-8068.2004	hsa04218	Cellular senescence	8878
SST	SMS	somatostatin	SST inhibits the secretion of pituitary hormones, including that of growth hormone/somatotropin (GH1), PRL, ACTH, luteinizing hormone (LH) and TSH.	others	Homo sapiens	Hypermethylation of BDNF and SST Genes in the Orbital Frontal Cortex of Older Individuals: A Putative Mechanism for Declining Gene Expression With Age	10.1038/npp.2015.107	hsa04935	Growth hormone synthesis, secretion and action	6750
SSTR3	Somatostatin Receptor 3; Somatostatin Receptor Type 3	somatostatin receptor 3	It have been associated with melanoma.	others	Homo sapiens	Expression of Somatostatin Receptors in Uveal Melanomas	10.1167/iovs.02-0481	hsa04935	Growth hormone synthesis, secretion and action	6753
STAT3	APRF; ADMIO1	signal transducer and activator of transcription 3 (acute-phase response factor)	Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors.	cellular senescence	Homo sapiens	Inhibition of JAK-STAT signaling stimulates adult satellite cell function	10.1038/nm.3655	hsa04935	Growth hormone synthesis, secretion and action	6774
STAT5A	STAT5; MGF	signal transducer and activator of transcription 5A	STAT5A carries out a dual function: signal transduction and activation of transcription. STAT5A mediates cellular responses to the cytokine KITLG/SCF and other growth factors.	cellular senescence	Homo sapiens	SOCS1 Regulates Senescence and Ferroptosis by Modulating the Expression of p53 Target Genes	10.18632/aging.101306	hsa04935	Growth hormone synthesis, secretion and action	6776
STAT5B	STAT5	signal transducer and activator of transcription 5B	STAT5B carries out a dual function: signal transduction and activation of transcription. STAT5B mediates cellular responses to the cytokine KITLG/SCF and other growth factors. STAT5B binds to the GAS element and activates PRL-induced transcription. STAT5B positively regulates hematopoietic/erythroid differentiation.	cellular senescence	Homo sapiens	Direct Targeting Options for STAT3 and STAT5 in Cancer	10.3390/cancers11121930	hsa04935	Growth hormone synthesis, secretion and action	6777
STK11	PJS; LKB1	serine/threonine kinase 11	STK11 appears to be involved in TP53-related apoptosis and regulates specific p53-dependent apoptosis pathways.	cellular senescence	Homo sapiens	The Peutz-Jegher Gene Product LKB1 Is a Mediator of p53-dependent Cell Death	10.1016/s1097-2765(01)00258-1	hsa04211	Longevity regulating pathway	6794
STUB1	Carboxy Terminus Of Hsp70-Interacting Protein	STIP1 homology and U-box containing protein 1, E3 ubiquitin protein ligase	E3 ubiquitin-protein ligase which targets misfolded chaperone substrates towards proteasomal degradation. STUB1 collaborates with ATXN3 in the degradation of misfolded chaperone substrates: ATXN3 restricting the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension. STUB1 may regulate myosin assembly in striated muscles together with UBE4B and VCP/p97 by targeting myosin chaperone UNC45B for proteasomal degradation. STUB1 mediates ubiquitination of RIPK3 leading to its subsequent proteasome-dependent degradation.	loss of proteostasis	Homo sapiens	CHIP/Stub1 functions as a tumor suppressor and represses NF-κB-mediated signaling in colorectal cancer	https://doi.org/10.1093/carcin/bgt393	unknown	Unknown	10273
SUMO1	PIC1; GMP1; SMT3C	small ubiquitin-like modifier 1	SUMO1 is a small protein that interacts with several partners and hence is related to many processes, including DNA repair and signal transduction.	genomic instability	Homo sapiens	SUMO suppresses and MYC amplifies transcription globally by regulating CDK9 sumoylation	10.1038/s41422-018-0023-9	unknown	Unknown	7341
SUN1	SUN Domain-Containing Protein 1	Sad1 and UNC84 domain containing 1	As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex involved in the connection between the nuclear lamina and the cytoskeleton. SUN1 is involved in telomere attachment to nuclear envelope in the prophase of meiosis implicating a SUN1/2:KASH5 LINC complex in which SUN1 and SUN2 seem to act at least partial redundantly. SUN1 is required for gametogenesis and involved in selective gene expression of coding and non-coding RNAs needed for gametogenesis. SUN1 may play a role in DNA repair by suppressing non-homologous end joining repair to facilitate the repair of DNA cross-links.	others	Homo sapiens	Telomere anchoring at the nuclear periphery requires the budding yeast Sad1-UNC-84 domain protein Mps3	10.1083/jcb.200706040	unknown	Unknown	23353
SYK	P72-Syk	Spleen Associated Tyrosine Kinase	Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates several biological processes including innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation and vascular development. Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains. The association with the receptor can also be indirect and mediated by adapter proteins containing ITAM or partial hemITAM domains. The phosphorylation of the ITAM domains is generally mediated by SRC subfamily kinases upon engagement of the receptor. More rarely signal transduction via SYK could be ITAM-independent. Direct downstream effectors phosphorylated by SYK include VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK.	NF-κB related gene	Homo sapiens	Caffeoyl-Prolyl-Histidine Amide Inhibits Fyn and Alleviates Atopic Dermatitis-Like Phenotypes via Suppression of NF-κB Activation	10.3390/ijms21197160	hsa04064	NF-kappa B signaling pathway	6850
TAB1	MAP3K7IP1	TGF-Beta Activated Kinase 1 (MAP3K7) Binding Protein 1	May be an important signaling intermediate between TGFB receptors and MAP3K7/TAK1. May play an important role in mammalian embryogenesis.	NF-κB related gene	Homo sapiens	Genome-Wide Association Transethnic Meta-Analyses Identifies Novel Associations Regulating Coagulation Factor VIII and von Willebrand Factor Plasma Levels	10.1161/CIRCULATIONAHA.118.034532	hsa04064	NF-kappa B signaling pathway	10454
TAB2	MAP3K7IP2	TGF-Beta Activated Kinase 1 (MAP3K7) Binding Protein 2	Adapter linking MAP3K7/TAK1 and TRAF6. Promotes MAP3K7 activation in the IL1 signaling pathway. The binding of 'Lys-63'-linked polyubiquitin chains to TAB2 promotes autophosphorylation of MAP3K7 at 'Thr-187'. Involved in heart development.	NF-κB related gene	Homo sapiens	Activation mechanism of c-Jun amino-terminal kinase in the course of neural differentiation of P19 embryonic carcinoma cells	10.1074/jbc.M406610200	hsa04064	NF-kappa B signaling pathway	23118
TAF1	NSCL2; TAFII250; KAT4;	TAF1 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 250kDa	TAF1 is essential in cell cycle progression and involved in transcription as part of the TFIID transcription factor together with TBP.	cellular senescence	Homo sapiens	The p250 subunit of native TATA box-binding factor TFIID is the cell-cycle regulatory protein CCG1	10.1038/362179a0	unknown	Unknown	6872
TBP	TFIID; GTF2D1; SCA17	TATA box binding protein	TBP is part of the TFIID general transcription factor. Because of its central role in the activation of eukaryotic genes, TBP is potentially involved in a large variety of processes.	genomic instability	Homo sapiens	RNA Polymerase II Transcription in Murine Cells Lacking the TATA Binding Protein	10.1126/science.1076327	unknown	Unknown	6908
TCF3	ITF1; E2A	transcription factor 3	Transcriptional regulator. TCF3 is involved in the initiation of neuronal differentiation. Heterodimers between TCF3 and tissue-specific basic helix-loop-helix (bHLH) proteins play major roles in determining tissue-specific cell fate during embryogenesis, like muscle or early B-cell differentiation.	cellular senescence	Homo sapiens	Hedgehog Signaling Maintains Hair Follicle Stem Cell Phenotype in Young and Aged Human Skin	10.1111/j.1474-9726.2009.00526.x	hsa04550	Signaling pathways regulating pluripotency of stem cells	6929
TERC	PFBMFT2; DKCA1	telomerase RNA component	Telomerase RNA component,involved in telomere maintenance as template in telomeric DNA synthesis,transcription up-regulated by endogeneous TERT.	telomere attrition	Homo sapiens	HuR Regulates Telomerase Activity Through TERC Methylation	10.1038/s41467-018-04617-7	unknown	Unknown	7012
TERF1	PIN2; TRF1; TRF	telomeric repeat binding factor (NIMA-interacting) 1	TRF1 is an essential component of shelterin, with important roles in telomere protection and telomere replication.	telomere attrition	Homo sapiens	Control of human telomere length by TRF1 and TRF2	10.1128/mcb.20.5.1659-1668.2000	unknown	Unknown	7013
TERF2	TRF2; TRBF2	telomeric repeat binding factor 2	TRF2 is essential for telomere capping owing to its roles in suppressing an ATM-dependent DNA damage response (DDR) at chromosome ends and inhibiting end-to-end chromosome fusions.	telomere attrition	Homo sapiens	TRF2 recruits the Werner syndrome (WRN) exonuclease for processing of telomeric DNA	10.1038/sj.onc.1206906	unknown	Unknown	7014
TERT	HEST2; TCS1	telomerase reverse transcriptase	Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.	telomere attrition	Homo sapiens	GWAS of Epigenetic Aging Rates in Blood Reveals a Critical Role for TERT	10.1038/s41467-017-02697-5	unknown	Unknown	7015
TFAP2A	AP-2; TFAP2; AP2TF	transcription factor AP-2 alpha (activating enhancer binding protein 2 alpha)	Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes.	genomic instability	Homo sapiens	Age related expression of Werner's syndrome protein in selected tissues and coexpression of transcription factors	10.1136/jcp.55.3.195	unknown	Unknown	7020
TFDP1	Dp-1; DRTF1; DP1	transcription factor Dp-1	TFDP1 is a transcription factor that may play a role in cell cycle regulation and apoptosis.	cellular senescence	Homo sapiens	Reduction of Total E2F/DP Activity Induces Senescence-Like Cell Cycle Arrest in Cancer Cells Lacking Functional pRB and p53	10.1083/jcb.200411093	hsa04110	Cell cycle	7027
TGFB1	CED; TGFbeta; TGFB	transforming growth factor, beta 1	The variability of the TGF-beta1 gene may affect longevity by playing a role in inflamm-aging.	altered intercellular communication	Homo sapiens	The G/C915 Polymorphism of Transforming Growth Factor beta1 Is Associated With Homo sapiens Longevity: A Study in Italian Centenarians	10.1111/j.1474-9728.2004.00129.x	hsa04218	Cellular senescence	7040
TICAM1	TRIF	Toll Like Receptor Adaptor Molecule 1	Functions as sorting adapter in different signaling pathways to facilitate downstream signaling leading to type I interferon induction. In TLR4 signaling, physically bridges TLR4 and TICAM1 and functionally transmits signal to TICAM1 in early endosomes after endocytosis of TLR4. In TLR2 signaling, physically bridges TLR2 and MYD88 and is required for the TLR2-dependent movement of MYD88 to endosomes following ligand engagement . Involved in IL-18 signaling and is proposed to function as a sorting adapter for MYD88 in IL-18 signaling during adaptive immune response . Forms a complex with RAB11FIP2 that is recruited to the phagosomes to promote the activation of the actin-regulatory GTPases RAC1 and CDC42 and subsequent phagocytosis of Gram-negative bacteria.	NF-κB related gene	Homo sapiens	Impact of age, BMI and HbA1c levels on the genome-wide DNA methylation and mRNA expression patterns in human adipose tissue and identification of epigenetic biomarkers in blood	10.1093/hmg/ddv124	hsa04064	NF-kappa B signaling pathway	148022
TIMP1	CLGI	TIMP Metallopeptidase Inhibitor 1	Metalloproteinase inhibitor that functions by forming one to one complexes with target metalloproteinases, such as collagenases, and irreversibly inactivates them by binding to their catalytic zinc cofactor. Acts on MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP11, MMP12, MMP13 and MMP16. Does not act on MMP14. Also functions as a growth factor that regulates cell differentiation, migration and cell death and activates cellular signaling cascades via CD63 and ITGB1. Plays a role in integrin signaling. Mediates erythropoiesis in vitro; but, unlike IL3, it is species-specific, stimulating the growth and differentiation of only human and murine erythroid progenitors.	loss of proteostasis	Homo sapiens	Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Extracellular Matrix Remodeling during Left Ventricular Diastolic Dysfunction and Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis	10.3390/ijms21186742	hsa04066	HIF-1 signaling pathway	7076
TIMP2	CSC-21K	TIMP Metallopeptidase Inhibitor 2	Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. Known to act on MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-13, MMP-14, MMP-15, MMP-16 and MMP-19.	senescence-associated secretory phenotype	Homo sapiens	The effect of aging in primary human dermal fibroblasts	10.1371/journal.pone.0219165	unknown	Unknown	7077
TIRAP	MyD88-2	TIR Domain Containing Adaptor Protein	Adapter involved in TLR2 and TLR4 signaling pathways in the innate immune response. Acts via IRAK2 and TRAF-6, leading to the activation of NF-kappa-B, MAPK1, MAPK3 and JNK, and resulting in cytokine secretion and the inflammatory response. Positively regulates the production of TNF-alpha and interleukin-6.	NF-κB related gene	Homo sapiens	Bidirectional, Temporal Associations of Sleep with Positive Events, Affect, and Stressors in Daily Life Across a Week	10.1007/s12160-016-9864-y	hsa04064	NF-kappa B signaling pathway	114609
TLR4	ARMD10	Toll Like Receptor 4	Cooperates with LY96 and CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) . Acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response . Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate, and Ni(2+). Responses triggered by Ni(2+) require non-conserved histidines and are, therefore, species-specific. Both M.tuberculosis HSP70 (dnaK) and HSP65 (groEL-2) act via this protein to stimulate NF-kappa-B expression.	NF-κB related gene	Homo sapiens	DUSP facilitates RPMI8226 myeloma cell aging and inhibited TLR4 expression	10.26355/eurrev_201809_15939	hsa04064	NF-kappa B signaling pathway	7099
TMEM67	Meckelin	Transmembrane Protein 67	Required for ciliary structure and function. Part of the tectonic-like complex which is required for tissue-specific ciliogenesis and may regulate ciliary membrane composition (By similarity). Involved in centrosome migration to the apical cell surface during early ciliogenesis. Involved in the regulation of cilia length and appropriate number through the control of centrosome duplication. Required for cell branching morphology. Essential for endoplasmic reticulum-associated degradation (ERAD) of surfactant protein C (SFTPC).	others	Homo sapiens	Hydrocephalus in a rat model of Meckel Gruber syndrome with a TMEM67 mutation	10.1038/s41598-018-37620-5	unknown	Unknown	91147
TNF	TNFSF2; DIF; TNF-alpha	tumor necrosis factor	A cytokine involved in the immune response, TNF can induce cell death in some tumour cells. It can also induce cellular proliferation and differentiation.	altered intercellular communication	Homo sapiens	The tumor necrosis factor alpha -308G>A polymorphism is associated with dementia in the oldest old	10.1111/j.1532-5415.2004.52369.x	hsa04150	mTOR signaling pathway	7124
TNFAIP3	Zinc Finger Protein A20	TNF Alpha Induced Protein 3	Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities. Involved in immune and inflammatory responses signaled by cytokines, such as TNF-alpha and IL-1 beta, or pathogens via Toll-like receptors (TLRs) through terminating NF-kappa-B activity. Essential component of a ubiquitin-editing protein complex, comprising also RNF11, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signaling pathways. In cooperation with TAX1BP1 promotes disassembly of E2-E3 ubiquitin protein ligase complexes in IL-1R and TNFR-1 pathways; affected are at least E3 ligases TRAF6, TRAF2 and BIRC2, and E2 ubiquitin-conjugating enzymes UBE2N and UBE2D3. In cooperation with TAX1BP1 promotes ubiquitination of UBE2N and proteasomal degradation of UBE2N and UBE2D3.	NF-κB related gene	Homo sapiens	TNFAIP3 Plays a Role in Aging of the Hematopoietic System	10.3389/fimmu.2020.536442	hsa04064	NF-kappa B signaling pathway	7128
TNFRSF10C	TRID	TNF Receptor Superfamily Member 10c	Receptor for the cytotoxic ligand TRAIL. Lacks a cytoplasmic death domain and hence is not capable of inducing apoptosis. May protect cells against TRAIL mediated apoptosis by competing with TRAIL-R1 and R2 for binding to the ligand.	senescence-associated secretory phenotype	Homo sapiens	CSF protein changes associated with hippocampal sclerosis risk gene variants highlight impact of GRN/PGRN	10.1016/j.exger.2017.01.025	hsa04060	Cytokine-cytokine receptor interaction	8794
TNFRSF11A	RANK	TNF Receptor Superfamily Member 11a	Receptor for TNFSF11/RANKL/TRANCE/OPGL; essential for RANKL-mediated osteoclastogenesis. Involved in the regulation of interactions between T-cells and dendritic cells.	NF-κB related gene	Homo sapiens	A genome-wide association study of myasthenia gravis	10.1001/jamaneurol.2014.4103	hsa04064	NF-kappa B signaling pathway	8792
TNFRSF11B	Osteoprotegerin	TNF Receptor Superfamily Member 11b	Acts as decoy receptor for TNFSF11/RANKL and thereby neutralizes its function in osteoclastogenesis. Inhibits the activation of osteoclasts and promotes osteoclast apoptosis in vitro. Bone homeostasis seems to depend on the local ratio between TNFSF11 and TNFRSF11B. May also play a role in preventing arterial calcification. May act as decoy receptor for TNFSF10/TRAIL and protect against apoptosis. TNFSF10/TRAIL binding blocks the inhibition of osteoclastogenesis.	others	Homo sapiens	Melatonin-micronutrients Osteopenia Treatment Study (MOTS): a translational study assessing melatonin, strontium (citrate), vitamin D3 and vitamin K2 (MK7) on bone density, bone marker turnover and health related quality of life in postmenopausal osteopen	10.18632/aging.101158	hsa04060	Cytokine-cytokine receptor interaction	4982
TNFRSF13C	CD268	TNF Receptor Superfamily Member 13C	B-cell receptor specific for TNFSF13B/TALL1/BAFF/BLyS. Promotes the survival of mature B-cells and the B-cell response.	NF-κB related gene	Homo sapiens	Recurrent respiratory tract infections (RRTI) in the elderly: A late onset mild immunodeficiency?	10.1016/j.clim.2017.05.008	hsa04064	NF-kappa B signaling pathway	115650
TNFRSF1A	TNF-R-I	TNF Receptor Superfamily Member 1A	Receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase.	senescence-associated secretory phenotype	Homo sapiens	Sulforaphane alleviates cadmium-induced toxicity in human mesenchymal stem cells through POR and TNFSF10 genes expression	10.1016/j.biopha.2019.108896	hsa04010	MAPK signaling pathway	7132
TNFRSF1B	TNFBR	TNF Receptor Superfamily Member 1B	Receptor with high affinity for TNFSF2/TNF-alpha and approximately 5-fold lower affinity for homotrimeric TNFSF1/lymphotoxin-alpha. The TRAF1/TRAF2 complex recruits the apoptotic suppressors BIRC2 and BIRC3 to TNFRSF1B/TNFR2. This receptor mediates most of the metabolic effects of TNF-alpha. Isoform 2 blocks TNF-alpha-induced apoptosis, which suggests that it regulates TNF-alpha function by antagonizing its biological activity.	senescence-associated secretory phenotype	Homo sapiens	Association of TNF Receptor 2 and CRP with GFR Decline in the General Nondiabetic Population	10.2215/CJN.09280916	hsa04060	Cytokine-cytokine receptor interaction	7133
TNFSF11	RANKL	TNF Superfamily Member 11	Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy. Induces osteoclastogenesis by activating multiple signaling pathways in osteoclast precursor cells, chief among which is induction of long lasting oscillations in the intracellular concentration of Ca (2+) resulting in the activation of NFATC1, which translocates to the nucleus and induces osteoclast-specific gene transcription to allow differentiation of osteoclasts. During osteoclast differentiation, in a TMEM64 and ATP2A2-dependent manner induces activation of CREB1 and mitochondrial ROS generation necessary for proper osteoclast generation.	NF-κB related gene	Homo sapiens	Melatonin-micronutrients Osteopenia Treatment Study (MOTS): a translational study assessing melatonin, strontium (citrate), vitamin D3 and vitamin K2 (MK7) on bone density, bone marker turnover and health related quality of life in postmenopausal osteopen	10.18632/aging.101158	hsa04064	NF-kappa B signaling pathway	8600
TNFSF13B	BAFF	TNF Superfamily Member 13	Cytokine that binds to TNFRSF13B/TACI and TNFRSF17/BCMA. TNFSF13/APRIL binds to the same 2 receptors. Together, they form a 2 ligands -2 receptors pathway involved in the stimulation of B- and T-cell function and the regulation of humoral immunity. A third B-cell specific BAFF-receptor (BAFFR/BR3) promotes the survival of mature B-cells and the B-cell response.	NF-κB related gene	Homo sapiens	Overexpression of the Cytokine BAFF and Autoimmunity Risk	10.1056/NEJMoa1610528	hsa04064	NF-kappa B signaling pathway	10673
TNFSF14	HVEM-L	TNF Superfamily Member 14	Cytokine that binds to TNFRSF3/LTBR. Binding to the decoy receptor TNFRSF6B modulates its effects. Acts as a ligand for TNFRSF14/HVEM  . Upon binding to TNFRSF14/HVEM, delivers costimulatory signals to T cells, leading to T cell proliferation and IFNG production .	NF-κB related gene	Homo sapiens	LIGHT/TNFSF14 is increased in patients with type 2 diabetes mellitus and promotes islet cell dysfunction and endothelial cell inflammation in vitro	10.1007/s00125-016-4036-y	hsa04064	NF-kappa B signaling pathway	8740
TOP1	DNA Topoisomerase I; Topoisomerase (DNA) I; DNA Topoisomerase 1	topoisomerase (DNA) I	TOP1 may also be important in the regulation of various brain functions and its activity is age-dependent.	others	Homo sapiens	Telomeric DNA damage by topoisomerase I. A possible mechanism for cell killing by camptothecin	10.1074/jbc.M309779200	unknown	Unknown	7150
TOP2A	DNA Topoisomerase II Alpha; Topoisomerase (DNA) II Alpha 170kDa; TP2A	topoisomerase (DNA) II alpha	RECQL5 co-localizes with Topoisomerase IIα during S-phase of the cell cycle. Cells with stable depletions of RECQL5 display a slow proliferation rate, a G2/M cell cycle arrest and late S-phase cycling defects.	cellular senescence	Homo sapiens	RECQL5 Cooperates With Topoisomerase II Alpha in DNA Decatenation and Cell Cycle Progression	10.1093/nar/gkr844	unknown	Unknown	7153
TOP2B	DNA Topoisomerase II Beta; Topoisomerase (DNA) II Beta 180kDa; TOPIIB	topoisomerase (DNA) II beta	Enzymatically it catalyzes ATP-dependent topological changes of double stranded DNA, while as a protein it was reported to be associated with several factors in promoting cell growth, migration, DNA repair and transcription regulation.	others	Homo sapiens	Topoisomerase IIβ and Its Role in Different Biological Contexts	10.1016/j.abb.2017.06.021	unknown	Unknown	7155
TOP3B	DNA Topoisomerase III Beta; TOP3B1; Topoisomerase (DNA) III Beta	topoisomerase (DNA) III beta	Mice lacking DNA topoisomerase 3beta are predisposed to a shortened lifespan, infertility, and lesions in multiple organs resulting from inflammatory responses.	altered intercellular communication	Homo sapiens	Topoisomerase 3β is the major topoisomerase for mRNAs and linked to neurodevelopment and mental dysfunction	10.1093/nar/gkw1293	unknown	Unknown	8940
TOPORS	Topoisomerase I-Binding RING Finger Protein	E3 ubiquitin-protein ligase Topors	TOPORS functions as an E3 ubiquitin-protein ligase and as an E3 SUMO1-protein ligase. TOPORS may regulate chromatin modification through sumoylation of several chromatin modification-associated proteins. TOPORS may be involved in DNA damage-induced cell death through IKBKE sumoylation.	loss of proteostasis	Homo sapiens	Topors functions as an E3 ubiquitin ligase with specific E2 enzymes and ubiquitinates p53	10.1074/jbc.C400300200	unknown	Unknown	10210
TP53	BMFS5; TRP53	tumor protein p53	TP53 acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. TP53 is involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process.	others	Homo sapiens	Variation in the human TP53 gene affects old age survival and cancer mortality	10.1016/j.exger.2004.10.001	hsa04211	Longevity regulating pathway	7157
TP53BP1	TP53-Binding Protein 1	tumor protein p53 binding protein 1	Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis. TP53BP1 plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1. TP53BP1 participates in the repair and the orientation of the broken DNA ends during CSR.	genomic instability	Homo sapiens	53BP1, a Mediator of the DNA Damage Checkpoint	10.1126/science.1076182	unknown	Unknown	7158
TP63	P73L; P63	tumor protein p63	TP63 acts as a sequence specific DNA binding transcriptional activator or repressor. TP63 may be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes. TP63 is involved in Notch signaling by probably inducing JAG1 and JAG2. TP63 plays a role in the regulation of epithelial morphogenesis.	genomic instability	Homo sapiens	p63, a p53 Homolog at 3q27-29, Encodes Multiple Products With Transactivating, Death-Inducing, and Dominant-Negative Activities	10.1016/s1097-2765(00)80275-0	unknown	Unknown	8626
TP73	P53-Like Transcription Factor	tumor protein p73	TP73 participates in the apoptotic response to DNA damage. TP73 isoforms containing the transactivation domain are pro-apoptotic, isoforms lacking the domain are anti-apoptotic and block the function of p53 and transactivating p73 isoforms. TP73 may be a tumor suppressor protein.	genomic instability	Homo sapiens	Human DeltaNp73 regulates a dominant negative feedback loop for TAp73 and p53	10.1189/jlb.1A0317-132R	hsa04115	p53 signaling pathway	7161
TPP2	Tripeptidyl Aminopeptidase	tripeptidyl peptidase II	Component of the proteolytic cascade acting downstream of the 26S proteasome in the ubiquitin-proteasome pathway. TRAP1 may be able to complement the 26S proteasome function to some extent under conditions in which the latter is inhibited.	loss of proteostasis	Homo sapiens	Generation of major histocompatibility complex class I antigens: functional interplay between proteasomes and TPPII	10.1038/ni1090	unknown	Unknown	7174
TRADD	Tumor Necrosis Factor Receptor Type 1 Associated Death Domain Protein	TNFRSF1A Associated Via Death Domain	The nuclear form acts as a tumor suppressor by preventing ubiquitination and degradation of isoform p19ARF/ARF of CDKN2A by TRIP12: acts by interacting with TRIP12, leading to disrupt interaction between TRIP12 and isoform p19ARF/ARF of CDKN2A (By similarity). Adapter molecule for TNFRSF1A/TNFR1 that specifically associates with the cytoplasmic domain of activated TNFRSF1A/TNFR1 mediating its interaction with FADD. Overexpression of TRADD leads to two major TNF-induced responses, apoptosis and activation of NF-kappa-B.	NF-κB related gene	Homo sapiens	Modulating TRADD to restore cellular homeostasis and inhibit apoptosis	10.1038/s41586-020-2757-z	hsa04064	NF-kappa B signaling pathway	8717
TRAF1	EBI6	TNF Receptor Associated Factor 1	Adapter molecule that regulates the activation of NF-kappa-B and JNK. Plays a role in the regulation of cell survival and apoptosis. The heterotrimer formed by TRAF1 and TRAF2 is part of a E3 ubiquitin-protein ligase complex that promotes ubiquitination of target proteins, such as MAP3K14. The TRAF1/TRAF2 complex recruits the antiapoptotic E3 protein-ubiquitin ligases BIRC2 and BIRC3 to TNFRSF1B/TNFR2.	NF-κB related gene	Homo sapiens	Traf1 induction and protection from tumor necrosis factor by nuclear factor-kappaB p65 is independent of serine 536 phosphorylation	10.1158/0008-5472.CAN-07-0922	hsa04064	NF-kappa B signaling pathway	7185
TRAF2	TRAP3	TNF Receptor Associated Factor 2	Regulates activation of NF-kappa-B and JNK and plays a central role in the regulation of cell survival and apoptosis. Required for normal antibody isotype switching from IgM to IgG. Has E3 ubiquitin-protein ligase activity and promotes 'Lys-63'-linked ubiquitination of target proteins, such as BIRC3, RIPK1 and TICAM1. Is an essential constituent of several E3 ubiquitin-protein ligase complexes, where it promotes the ubiquitination of target proteins by bringing them into contact with other E3 ubiquitin ligases. Regulates BIRC2 and BIRC3 protein levels by inhibiting their autoubiquitination and subsequent degradation; this does not depend on the TRAF2 RING-type zinc finger domain. Plays a role in mediating activation of NF-kappa-B by EIF2AK2/PKR. In complex with BIRC2 or BIRC3, promotes ubiquitination of IKBKE.	NF-κB related gene	Homo sapiens	Bone Remodeling and the Role of TRAF3 in Osteoclastic Bone Resorption	10.3389/fimmu.2018.02263	hsa04064	NF-kappa B signaling pathway	7186
TRAF3	LAP1	TNF Receptor Associated Factor 3	Regulates pathways leading to the activation of NF-kappa-B and MAP kinases, and plays a central role in the regulation of B-cell survival. Part of signaling pathways leading to the production of cytokines and interferon. Required for normal antibody isotype switching from IgM to IgG. Plays a role T-cell dependent immune responses. Plays a role in the regulation of antiviral responses. Is an essential constituent of several E3 ubiquitin-protein ligase complexes. May have E3 ubiquitin-protein ligase activity and promote 'Lys-63'-linked ubiquitination of target proteins. Inhibits activation of NF-kappa-B in response to LTBR stimulation. Inhibits TRAF2-mediated activation of NF-kappa-B. Down-regulates proteolytic processing of NFKB2, and thereby inhibits non-canonical activation of NF-kappa-B. Promotes ubiquitination and proteasomal degradation of MAP3K14.	NF-κB related gene	Homo sapiens	Bone Remodeling and the Role of TRAF3 in Osteoclastic Bone Resorption	10.3389/fimmu.2018.02263	hsa04064	NF-kappa B signaling pathway	7187
TRAF6	RNF85	TNF Receptor Associated Factor 6	E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as IKBKG, IRAK1, AKT1 and AKT2. Also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation. Leads to the activation of NF-kappa-B and JUN. May be essential for the formation of functional osteoclasts. Seems to also play a role in dendritic cells (DCs) maturation and/or activation. Represses c-Myb-mediated transactivation, in B-lymphocytes. Adapter protein that seems to play a role in signal transduction initiated via TNF receptor, IL-1 receptor and IL-17 receptor. Regulates osteoclast differentiation by mediating the activation of adapter protein complex 1 (AP-1) and NF-kappa-B, in response to RANK-L stimulation. Together with MAP3K8, mediates CD40 signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production.	NF-κB related gene	Homo sapiens	Gain-of-Function Mutation of Card14 Leads to Spontaneous Psoriasis-like Skin Inflammation through Enhanced Keratinocyte Response to IL-17A	10.1016/j.immuni.2018.05.012	hsa04064	NF-kappa B signaling pathway	7189
TRAP1	TNFR-Associated Protein 1	TNF receptor-associated protein 1	TRAP1 is a chaperone that expresses an ATPase activity. TRAP1 is involved in maintaining mitochondrial function and polarization, downstream of PINK1 and mitochondrial complex I. TRAP1 is a negative regulator of mitochondrial respiration able to modulate the balance between oxidative phosphorylation and aerobic glycolysis.	mitochondrial dysfunction	Homo sapiens	e mitochondrial chaperone TRAP1 promotes neoplastic growth by inhibiting succinate dehydrogenase	10.1016/j.cmet.2013.04.019	unknown	Unknown	10131
TRIM25	RNF147	Tripartite Motif Containing 25	unctions as a ubiquitin E3 ligase and as an ISG15 E3 ligase . Involved in innate immune defense against viruses by mediating ubiquitination of DDX58 and IFIH1. Mediates 'Lys-63'-linked polyubiquitination of the DDX58 N-terminal CARD-like region and may play a role in signal transduction that leads to the production of interferons in response to viral infection . Mediates 'Lys-63'-linked polyubiquitination of IFIH1 . Promotes ISGylation of 14-3-3 sigma (SFN), an adapter protein implicated in the regulation of a large spectrum signaling pathway . Mediates estrogen action in various target organs . Mediates the ubiquitination and subsequent proteasomal degradation of ZFHX3 .	NF-κB related gene	Homo sapiens	TRIM25 has a dual function in the p53/Mdm2 circuit	10.1038/onc.2015.21	hsa04064	NF-kappa B signaling pathway	7706
TRPS1	GC79	Transcriptional Repressor GATA Binding 1	Transcriptional repressor. Binds specifically to GATA sequences and represses expression of GATA-regulated genes at selected sites and stages in vertebrate development. Regulates chondrocyte proliferation and differentiation. Executes multiple functions in proliferating chondrocytes, expanding the region of distal chondrocytes, activating proliferation in columnar cells and supporting the differentiation of columnar into hypertrophic chondrocytes.	others	Homo sapiens	The RING finger protein RNF4, a co-regulator of transcription, interacts with the TRPS1 transcription factor.	10.1074/jbc.M306259200	unknown	Unknown	7227
TRPV1	Vanilloid Receptor Subtype 1	transient receptor potential cation channel subfamily V member 1	TRPV1 is involved in mediation of inflammatory pain and hyperalgesia. TRPV1 is sensitized by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases, which involves PKC isozymes and PCL. TRPV1 can be activated by endogenous compounds, including 12-hydroperoxytetraenoic acid and bradykinin. TRPV1 acts as ionotropic endocannabinoid receptor with central neuromodulatory effects.	others	Homo sapiens	Molecular Determinants of Vanilloid Sensitivity in TRPV1	10.1074/jbc.M312577200	unknown	Unknown	7442
TSC1	Tuberous Sclerosis 1	Hamartin	In complex with TSC2, TSC1 inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling. TSC1 is involved in microtubule-mediated protein transport, but this seems to be due to unregulated mTOR signaling. TSC1 acts as a co-chaperone for HSP90AA1 facilitating HSP90AA1 chaperoning of protein clients such as kinases, TSC2 and glucocorticoid receptor NR3C1.	deregulated nutrient sensing	Homo sapiens	Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling	10.1073/pnas.202476899	hsa04211	Longevity regulating pathway	7248
TSC2	Tuberous Sclerosis 2	Tuberin	In complex with TSC1, this tumor suppressor inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling. TSC2 acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1. TSC2 may also play a role in microtubule-mediated protein transport.	deregulated nutrient sensing	Homo sapiens	Tuberous sclerosis complex-1 and -3 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling	10.1073/pnas.202476900	hsa04211	Longevity regulating pathway	7249
TXN	TRDX; ADF	thioredoxin	TXN participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions.	others	Homo sapiens	The role of thioredoxin in the aging process: involvement of oxidative stress	10.1089/152308603770310211	unknown	Unknown	7295
UBB	HEL-S-50	ubiquitin B	UBB exists either covalently attached to another protein, or free (unanchored).	loss of proteostasis	Homo sapiens	Long-term Proteasomal Inhibition in Transgenic Mice by UBB(+1) Expression Results in Dysfunction of Central Respiration Control Reminiscent of Brainstem Neuropathology in Alzheimer Patients	10.1007/s00401-012-1003-7	hsa04137	Mitophagy - animal	7314
UBE2I	UBC9	ubiquitin-conjugating enzyme E2I	UBE2I catalyzes the attachment of SUMO1 to other proteins. It is related to PCNA, suggesting it might play a role in DNA repair and perhaps even in aging.	genomic instability	Homo sapiens	RAD6-dependent DNA Repair Is Linked to Modification of PCNA by Ubiquitin and SUMO	10.1038/nature00991	unknown	Unknown	7329
UCHL1	PGP9.5; Uch-L1; PARK5	ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase)	UCHL1 has both ligase and hydrolase activities, and it may be involved in protein degradation.	loss of proteostasis	Homo sapiens	The Neuron-Specific Protein PGP 9.5 Is a Ubiquitin Carboxyl-Terminal Hydrolase	10.1126/science.2530630	unknown	Unknown	7345
UCP1	Mitochondrial Brown Fat Uncoupling Protein 1	uncoupling protein 1 (mitochondrial, proton carrier)	UCP1 functions as a long-chain fatty acid/LCFA and proton symporter, simultaneously transporting one LCFA and one proton through the inner mitochondrial membrane. However, LCFAs remaining associated with the transporter via their hydrophobic tails, it results in an apparent transport of protons activated by LCFAs. UCP1 regulates the production of reactive oxygen species/ROS by mitochondria.	mitochondrial dysfunction	Homo sapiens	Expression, folding, and proton transport activity of human uncoupling protein-1 (UCP1) in lipid membranes: evidence for associated functional forms	10.1074/jbc.M113.509935	unknown	Unknown	7350
UCP2	Mitochondrial Uncoupling Protein 2; Solute Carrier Family 25 Member 8	uncoupling protein 2 (mitochondrial, proton carrier)	UCP are mitochondrial transporter proteins that create proton leaks across the inner mitochondrial membrane, thus uncoupling oxidative phosphorylation from ATP synthesis. As a result, energy is dissipated in the form of heat.	mitochondrial dysfunction	Homo sapiens	UCP2 transports C4 metabolites out of mitochondria, regulating glucose and glutamine oxidation	https://doi.org/10.1073/pnas.1317400111	unknown	Unknown	7351
UCP3	SLC25A9	uncoupling protein 3 (mitochondrial, proton carrier)	Mitochondrial uncoupling proteins create proton leaks across the inner mitochondrial membrane to uncouple oxidative phosphorylation from ATP synthesis resulting in energy being dissipated as heat.	mitochondrial dysfunction	Homo sapiens	Energy Metabolism in Uncoupling Protein 3 Gene Knockout Mice	10.1074/jbc.M910179199	unknown	Unknown	7352
ULK1	Serine/Threonine-Protein Kinase ULK1	Serine/threonine-protein kinase ULK1	ULK1 acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. ULK1 is part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. ULK1 is activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2 and PRKAG1, leading to negatively regulate AMPK activity.	others	Homo sapiens	Interaction of the Unc-51-like kinase and microtubule-associated protein light chain 3 related proteins in the brain: possible role of vesicular transport in axonal elongation	10.1016/s0169-328x(00)00218-7	hsa04211	Longevity regulating pathway	8408
VCAM1	CD106	Vascular Cell Adhesion Molecule 1	mportant in cell-cell recognition. Appears to function in leukocyte-endothelial cell adhesion. Interacts with integrin alpha-4/beta-1 (ITGA4/ITGB1) on leukocytes, and mediates both adhesion and signal transduction. The VCAM1/ITGA4/ITGB1 interaction may play a pathophysiologic role both in immune responses and in leukocyte emigration to sites of inflammation.	NF-κB related gene	Homo sapiens	Aged blood impairs hippocampal neural precursor activity and activates microglia via brain endothelial cell VCAM1	10.1038/s41591-019-0440-4	hsa04064	NF-kappa B signaling pathway	7412
VCP	TERA; P97	valosin containing protein	VCP is necessary for the fragmentation of Golgi stacks during mitosis and for their reassembly after mitosis. VCP is involved in the formation of the transitional endoplasmic reticulum (tER).	loss of proteostasis	Homo sapiens	VCP and PSMF1: Antagonistic Regulators of Proteasome Activity	10.1016/j.bbrc.2015.06.086	unknown	Unknown	7415
VEGFA	VEGF-A	vascular endothelial growth factor A	Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. VEGFA induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. VEGFA binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin.	others	Homo sapiens	Vascular endothelial growth factor induces cyclooxygenase-dependent proliferation of endothelial cells via the VEGF-2 receptor	10.1096/fj.00-0757fje	hsa04066	HIF-1 signaling pathway	7422
VEGFC	Flt4-L	Vascular Endothelial Growth Factor C	Growth factor active in angiogenesis, and endothelial cell growth, stimulating their proliferation and migration and also has effects on the permeability of blood vessels. May function in angiogenesis of the venous and lymphatic vascular systems during embryogenesis, and also in the maintenance of differentiated lymphatic endothelium in adults. Binds and activates KDR/VEGFR2 and FLT4/VEGFR3 receptors.	senescence-associated secretory phenotype	Homo sapiens	Signatures of photo-aging and intrinsic aging in skin were revealed by transcriptome network analysis	10.18632/aging.101496	hsa04010	MAPK signaling pathway	7424
WNT2	IRP	Wnt Family Member	Ligand for members of the frizzled family of seven transmembrane receptors. Functions in the canonical Wnt signaling pathway that results in activation of transcription factors of the TCF/LEF family (PubMed:20018874). Functions as upstream regulator of FGF10 expression. Plays an important role in embryonic lung development. May contribute to embryonic brain development by regulating the proliferation of dopaminergic precursors and neurons (By similarity).	senescence-associated secretory phenotype	Homo sapiens	SERPINH1 regulates EMT and gastric cancer metastasis via the Wnt/β-catenin signaling pathway	10.18632/aging.102831	hsa04150	mTOR signaling pathway	7472
WRN	RECQL2; RECQ3	Werner syndrome, RecQ helicase-like	Multifunctional enzyme that has both magnesium and ATP-dependent DNA-helicase activity and 3'->5' exonuclease activity towards double-stranded DNA with a 5'-overhang.	genomic instability	Homo sapiens	Aging Stem Cells. A Werner Syndrome Stem Cell Model Unveils Heterochromatin Alterations as a Driver of Homo sapiens Aging	10.1126/science.aaa1356	unknown	Unknown	7486
XIAP	IAP-Like Protein 1	X-Linked Inhibitor Of Apoptosis	Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, copper homeostasis, mitogenic kinase signaling, cell proliferation, as well as cell invasion and metastasis. Acts as a direct caspase inhibitor. Directly bind to the active site pocket of CASP3 and CASP7 and obstructs substrate entry. Inactivates CASP9 by keeping it in a monomeric, inactive state. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and the target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, CASP3, CASP7, CASP8, CASP9, MAP3K2/MEKK2, DIABLO/SMAC, AIFM1, CCS and BIRC5/survivin. Ubiquitinion of CCS leads to enhancement of its chaperone activity toward its physiologic target, SOD1, rather than proteasomal degradation. Ubiquitinion of MAP3K2/MEKK2 and AIFM1 does not lead to proteasomal degradation.	NF-κB related gene	Homo sapiens	Elevated X-linked inhibitor of apoptosis protein (XIAP) expression uncovers detrimental prognosis in subgroups of neoadjuvant treated and T-cell rich esophageal adenocarcinoma	10.1186/s12885-019-5722-1	hsa04064	NF-kappa B signaling pathway	331
XPA	XPAC; XP1	xeroderma pigmentosum, complementation group A	XPA is primarily involved in DNA repair. The XPA protein functions in the recognition of DNA damage.	genomic instability	Homo sapiens	Xeroderma Pigmentosa Group A (XPA), Nucleotide Excision Repair and Regulation by ATR in Response to Ultraviolet Irradiation	10.1007/978-3-319-56017-5_4	unknown	Unknown	7507
XRCC5	KU80; KARP-1; Ku86	X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining)	The DNA repair protein Ku (a heterodimer of Ku70 and Ku80 subunits) associates with mammalian telomeres and contributes to telomere maintenance.	telomere attrition	Homo sapiens	Human Ku70/80 Associates Physically With Telomerase Through Interaction With hTERT	10.1074/jbc.M208542200	unknown	Unknown	7520
XRCC6	KU70; ML8; G22P1	X-ray repair complementing defective repair in Chinese hamster cells 6	Ku70 forms a heterodimer with Ku80, called Ku, that is critical for repairing DNA double-stand breaks by nonhomologous end joining and for maintaining telomeres. The Ku heterodimer is important for longevity assurance in mice.	others	Homo sapiens	Human Ku70/80 associates physically with telomerase through interaction with hTERT	10.1074/jbc.M208542200	unknown	Unknown	2547
YWHAZ	KCIP-1; 14-3-3-zeta; YWHAD	tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta	YWHAZ interacts with so many proteins, including many associated with ageing such as the?INS/IGF1?pathway, may be involved in stem cell development.	stem cell exhaustion	Homo sapiens	Proteomic Analysis Identifies That 14-3-3zeta Interacts With Beta-Catenin and Facilitates Its Activation by Akt	10.1073/pnas.0406499101	hsa04110	Cell cycle	7534
ZAP70	SRK	Zeta Chain Of T Cell Receptor Associated Protein Kinase 70	Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates motility, adhesion and cytokine expression of mature T-cells, as well as thymocyte development. Contributes also to the development and activation of primary B-lymphocytes. When antigen presenting cells (APC) activate T-cell receptor (TCR), a serie of phosphorylations lead to the recruitment of ZAP70 to the doubly phosphorylated TCR component CD247/CD3Z through ITAM motif at the plasma membrane. This recruitment serves to localization to the stimulated TCR and to relieve its autoinhibited conformation. Release of ZAP70 active conformation is further stabilized by phosphorylation mediated by LCK.	NF-κB related gene	Homo sapiens	Otud7b facilitates T cell activation and inflammatory responses by regulating Zap70 ubiquitination	10.1084/jem.20151426	hsa04064	NF-kappa B signaling pathway	7535
ZMPSTE24	FACE-1; Ste24p; STE24	zinc metallopeptidase STE24	ZMPSTE24 is a zinc metalloprotease involved in the post-translational processing of?LMNA?precursors. ZMPSTE24-null mice have a short lifespan and show some signs of accelerated ageing.	genomic instability	Homo sapiens	Loss of ZMPSTE24 (FACE-1) Causes Autosomal Recessive Restrictive Dermopathy and Accumulation of Lamin A Precursors	10.1093/hmg/ddi159	unknown	Unknown	10269