| dcp-66 | Deacetylase Complex Protein 66 | dcp-66 RNAi shortens the mean lifespan by 29% and suppresses lifespan extension by isp-1 mutation, but does not significantly affect lifespan extension neither by eat-2 nor daf-2 mutation [22829775]. | Nematode |
| ELOVL2 | elongation of very long chain fatty acids (FEN1/Elo2, SUR4/Elo3, yeast)-like 2 | In breast, kidney and lung tissues the makers cg23606718 and cg16867657 were commonly differentially methylated with age and both have been annotated to ELOVL2 [23177740], which is linked to photoaging response in human skin [20514327]. | Human |
| Ercc2 | Excision repair cross-complementing rodent repair deficiency, complementation group 2 | Mutations in Ercc2 increases cancer incidence and appear to accelerate ageing. Homozyogus mutation of Ercc2 results in an extreme shortening (71%) of lifespan (mean lifespan = 7 months) relative to wild-type (mean lifespan = 24 months) [de Boer et al. 2002]. The shortened lifespan of the mutant mouse is accompanied by symptoms of premature aging including osteoporosis, early greying, cahexia, and infertility. It provides a mouse model for the britte hair disorder trichothiodystrophy (TTD) as it phenotypes include britte hair, UV sensitivity, and developmental defects [9651581]. | House mouse |
| Ercc4 | Excision repair cross-complementing rodent repair deficiency, complementation group 4 | ERCC4-ERCC1-deficient mice exhibit signs of premature aging [17183314]. | House mouse |
| EXO1 | exonuclease 1 | The rs1776180 C allele in the promoter of EXO1 is significantly enriched in female Germans centenarians and this can be replicated in 445 female French centenarians. The C allele leads to the loss of binding site for the basic helix-loop-helix transcription factor E47, resulting in higher EXO1 expression [19698732].EXO1 was found to be associated with longevity [19698732]. EXO1 was not found to be associated with longevity [23770741]. | Human |
| FAR11 | Factor ARrest 3 | Deletion of FAR11 significantly reduces mean chronological lifespan under starvation/extreme DR relatively to wild-type [20657825]. | Budding yeast |
| FAR3 | Factor ARrest 3 | Deletion of FAR3 significantly reduces mean chronological lifespan under starvation/extreme DR relatively to wild-type [20657825]. | Budding yeast |
| FCY1 | FluoroCYtosine resistance 1 | Deletion of FCY1 does non-significantly decrease mean and maximum replicative lifespan by 4% and 8%, respectively [20550517]. | Budding yeast |
| Foxm1 | Forkhead box M1 | Deletion of Foxm1 causes age-related deterioration in liver regeneration. Increased hepatocyte expression in 12-month-old (aged) transgenic mice of Foxm1b alone is sufficient to restore hepatocyte proliferation to levels found in 2-month-old (young) regenerating liver [14647066]. | House mouse |
| Foxo3 | — | — | House mouse |
| GCN4 | Transcriptional activator of amino acid biosynthetic genes in response to amino acid starvation; expression is tightly regulated at both the transcriptional and translational levels | Deletion of GCN4 increases the replicative lifespan by 10% in the alpha strain [19030232].
GCN4 deletion decreases the lifespan in the alpha and a strain [20657825].
The chronological lifespan of GCN4 deletion is strongly decreased in the a strain [20421943]. | Budding yeast |
| GH1 | Growth hormone 1 | Transgenic mice overexpressing bovine GH1 are bigger than controls and display early onset of pathological changes in the kidneys such glomerulosis and glomerulonephritis as well as signs of premature aging such as a shortened lifespan, increased astrogliosis, shortened reproductive lifepsan and early onset of age-related changes in cognitive function, hypothalamic neurotransmitter turnover, and plasma corticosterone levels [14583653]. | Cattle |
| GHR | growth hormone receptor | Individuals with low GH/IGF-I signaling due to a defect in the growth hormone receptor (GHR) are protected against cancer. Among the human individuals with a defect in GHR no cancer deaths were observed. GHR deficiency does not appear to extend lifespan because it is associated with increased risk of heart disease [21325617]. Variants in GHR were found to be associated with longevity [19489743]. | Human |
| GTPBP10 | GTP-binding protein 10 (putative) | Age-related differential methylation of the genetic marker rs42663, which is missense mutation in GTPBP10 is statistically significant association with age and aging rate. GTPB10 associates with cg27367526 in STEAP2 [23177740]. | Human |
| H2S | Hydrogen Sulfide | Hydrogen sulfide (H2S) is a colorless, poisonousness, flammable gas with the characteristic foul odor of rotten eggs. A few breath of air containing high levels H2S can cause death, while lower long-term exposure can cause eye irritation, headache, and fatigue.
The human body produces small amounts of hydrogen sulfide and uses it as signaling molecule. It has a variety of physiological effects. For instance, it relaxes the vascular endothelium and smooth muscle cells, which is important to maintaining clean arteries as one ages. It is an important signaling molecule because of its significant effects on the cardiovascular and nervous systems.
Hydrogen sulfide appears to slow aging by inhibiting free-radical reactions via the activation of SIRT1 and probably through its Interactions with Klotho.
Klotho seems to be upregulated by hydrogen sulfide and extends lifespan via a number of different pathways, some of which promote production of endogenous antioxidants.
H2S produced in the kidneys has direct angiotension-converting enzyme (ACE) inhibiting activity. It is therefore an ACE inhibitor, just like certain drugs that mitigate high blood pressure.
Plasma hydrogen sulfide declines with age and is lower in spontaneously hypertensive rats. A lack of hydrogen peroxide is in general implicated in cardiovascular disease. Declining hydrogen sulfide levels also underline neurological health. Endogenous hydrogen sulfide is lower in animal model of Parkinson disease and depressed in the brains of patients with Alzheimer's disease. Hydrogen sulfide may also protective in animal models as well as humans against cancer [23297346]. | — |
| HCFC1 | host cell factor C1 (VP16-accessory protein) | HCFC1 is a cronserved protein with a predominant nuclear localisation [7876203]. The mammalian HCF-1 is involved in cell cycle progression, both at the G1/S transition and at M phase and cytokinesis [12743030 ;15200950;17612494]. It acts by binding to and regulating many different transcripts and chromatin factors and assembling appropriate protein complexes for context-dependent gene expression regulation. HCF-1 helps to recruit the activating Set1/Ash2 histone methyltransferase complex [18043729]. Mammalian HCF-1 recruits te Set1/Ash2 histone methyltransferase activating complex to E2F1 and the Sin3 histone deacetylase repressive complex to E2F4 at the appropriate time of the cell cycle, which is likely to reinforce the activating or repressive functions of the respective E2F family members [17612494]. | Human |
| HNRNPD | eterogeneous nuclear ribonucleoprotein D (AU-rich element RNA binding protein 1, 37kDa) | HNRNPD controls inflammation by turning off the inflammatory response to stop the onset of septic shock. Cessation of inflammatory cytokine respisne is mediated partly through cytokine mRNA degradation facilitated by RNA-binding proteins, including HNRNPD. HNRNPD deletion leads to accelerated aging as evidenced by strinking telomere erosion, markedly increased DNA damage repsosne at telomere ends, pronounced cellular senescence and rapid premature aging that increases with successive generations. HNRNPD which is a family of four related genes also maintains the integrity of chromosomes by activating telomerase, because HNRNPD strongly activates the transcription promoter for Tert [Pont et al., 2012]. | House mouse |
| IDP3 | Isocitrate Dehydrogenase, NADP-specific 3 | Deletion of IDP3 results in a replicative lifespan increase by 15% in the alpha strain and decrease by 20% in the a strain [18340043; 19030232]. | Budding yeast |
| IL6 | interleukin 6 (interferon, beta 2) | Elevated IL-6 serum levels are associated with diseases, disability and mortality in the elderly. The proportion of homozyogtes for the G allele at -174 locus (a promoter genetic variability) decreases centenarian males, but not centenarians females. Only males, homozygous for the G allele at -174 locus have higher IL6- serum levels. Individuals who are genetically predisposed to produce high levels of IL-6 during aging (i.e. -174 locus GG homozygous men) are disadvantaged for longevity [11500818]. | Human |
| IL6 | interleukin 6 (interferon, beta 2) | — | Human |
| IMD2 | IMP Dehydrogenase 2 | Deletion of IMD2 does non-significantly decrease mean replicative lifespan by 1% and non-significantly increased maximum replicative lifespan by 21% [20550517]. | Budding yeast |
| INP54 | Phosphatidylinositol 4,5-bisphosphate 5-phosphatase with a role in secretion, localizes to the endoplasmic reticulum via the C-terminal tail; lacks the Sac1 domain and proline-rich region found in the other 3 INP proteins | Replicative lifespan increased by 15% in the alpha strain and decreased by 15% in the a strain | Budding yeast |
| JAKMIP3 | Janus kinase and microtubule interacting protein 3 | Age-related differential methylation of the genetic marker rs2818384 which is synonymous to the mutation in JAKMIP3 is statistically significant association with age and aging rate. JAKMIP3 has a *cis* association with the aging differential methylated marker cg05652533 [23177740].
Copy-number variants of JAKMIP3 are associated with glioblastoma [Xiong et al. 2010].
Xiong, M., Dong, H., Siu, H., Peng, G., Wang, Y., and Jin, L. (2010). Genome-Wide Association Studies of Copy Number Variation in Glioblastoma. Proceedings of the 4th International Conference on Bioinformatics and Biomedical Engineering (iCBBE), 1–4.
| Human |
| KLF14 | Kruppel-like factor 14 | Six aging differentially methylated markers lay within KLF14 [23177740]. | Human |
| kri-1 | human KRIT 1 (Krev interaction trapped/cerebral cavernous malformation 1) homolog | RNA interference suppresses glp-1 life-extension but does not shorten lifespan of wildtype strains. kri-1(ok1251) mutation does not shorten the lifespan significantly [22560223]. | Nematode |
