| 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 |
| NMD4 | Nonsense-Mediated mRNA Decay 4 | Deletion of NMD4 increases replicative lifespan [16293764]. NMD4 deletion results in replicative lifespan increase by 25% in the alpha strain and decrease by 20% in a strain [19030232]. | Budding yeast |
| SML1 | Suppressor of Mec1 Lethality 1 | Deletion of SML1 increases non-significantly mean replicative lifespan by 3% and non-significantly maximum lifespan by 16% [20550517]. | Budding yeast |
| TAD1 | tRNA-specific Adenosine Deaminase 1 | Deletion of TAD1 does non-significantly increase the mean replicative lifespan by 14% [20550517]. | Budding yeast |
| TPK2 | Takashi's Protein Kinase 2 | Deletion of TPK2 in a tpk1 and tpk3 double mutant background decreases PKA activity and extends replicative lifespan by approximately 25% in SGY446 strain [11000115]. | Budding yeast |
| YDR124W | — | Deletion of YDR124W increases replicative lifespan by 30% in the alpha and decreases lifespan by 10% in a strain [19030232]. | Budding yeast |
| ZTA1 | Zeta-crystallin homolog, found in the cytoplasm and nucleus; has similarity to E. coli quinone oxidoreductase and to human zeta-crystallin, which has quinone oxidoreductase activity | Deletion of ZTA1 increases replicative lifespan by 15% in the alpha strain and decreased by 10% in the a strain [18340043]. Although ZTA1 was identified as a potential long-lived mutant strain in a bar-code screen, deletion of ZTA1 does not significantly affect chronological lifespan under starvation/extreme DR [20657825]. | 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 |
| Ercc4 | Excision repair cross-complementing rodent repair deficiency, complementation group 4 | ERCC4-ERCC1-deficient mice exhibit signs of premature aging [17183314]. | House mouse |
| miR-214 | microRNA 214 | Expression increases with age in mouse liver. The miRNA downregulates detoxification and regeneration genes, which may contribute to aging [18561983]. | House mouse |
| Mir669c | microRNA 669c | Expression increases with age in mouse liver. The miRNA downregulates detoxification and regeneration genes, which may contribute to aging [18561983]. | House mouse |
| SAG12 | senescence-associated protein 12 | Expression of SAG12 is specifically activated by developmentally controlled senescence pathways but not by stress- or hormone-controlled pathways [10579486; 10579487]. | — |
| tert | telomerase reverse transcriptase | First-generation tert(-/-) zebrafish die prematurely with shorter telomeres. tert(-/-) fish develop degenerative phenotypes, including premature infertility, gastrointestinal atrophy, and sarcopenia. tert(-/-) mutants have impaired cell proliferation, accumulation of DNA damage markers, and a p53 response leading to early apoptosis, followed by accumulation of senescence cells. Apoptosis is primarily observed in the proliferative niche and germ cells. Cell proliferation, but not apoptosis, is rescued in tp53(-/-)tert(-/-) mutants, underscoring p53 as mediator of telomerase deficiency and consequent telomere instability [http://denigma.de/url/3p]. | Zebrafish |
| Rae1 | RAE1 RNA export 1 homolog (S. pombe) | Haploinsufficiency of Bub3 and Rae1, but not haploinsufficiency of either gene by itself, reduces lifespan by 12% and appears to accelerate ageing. | House mouse |
| Bub3 | budding uninhibited by benzimidazoles 3 homolog (S. cerevisiae) | Haploinsufficiency of Bub3 and Rae1, but not haploinsufficiency of either gene by itself, reduces lifespan by 12% and appears to accelerate aging [16476774]. | House mouse |
| 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 |
| 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]. | — |
| Mir27a | MicroRNA 27a | In Ames dwarf mice (which displays delayed Aging), Mir27a expression is significantly higher than in control mice. Mir27a may be responsible for delayed Aging in dwarf mice: it suppresses the expression of ODC1 and SRM, which in turn suppresses polyamine synthesis in dwarf mice liver. Part of the ability of dwarf mice to suppress or avoid tumor or Cancer growth may be attributed to the decreased Polyamine biosynthesis. [19878148] | House mouse |
| 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 |
| bax | Bcl2-associated X protein | Inactivation of proapoptotic Bax extends fertile potential and minimized age-related health problems, including bone and muscle loss, excess fat deposition, alopecia, cataracts, deafness, increased anxiety, and selective attention deficit. Bax deficiency does not lead to an increase in tumor incidence. Despite the apparently increased quality of life of aging females lacing Bax, there is no significant differences in overall lifespan [17360389]. | House mouse |
| Mir34a | microRNA mir-34a | Increases in aging rat liver, which suppresses the expression of such proteins as Sirt1 and Mgst1, resulting in dysfunction of oxidative stress defense and regulation [21216258] | Norway rat |
| Mir93 | microRNA mir-93 | Increases in Aging rat Liver, which suppresses the expression of such proteins as Sirt1 and Mgst1, resulting in dysfunction of oxidative stress defense and regulation [21216258] | Norway rat |
| 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 |
| Nos3 | nitric oxide synthase 3, endothelial cell | Knockout males exhibited premature death and age-related cardiac dysfunction but not females. | House mouse |
