| cert | ceramide transfer protein | cert mutants exhibit a shortened lifespan accompanied by enhanced oxidative damage to cellular proteins and metabolic compromise, such as increasing glucose levels, reminiscent of premature aging [17592126]. | Fruit fly |
| CHL1 | CHromosome Loss 1 | CHL1 deletion mutant exhibits a shortened mean and maximum lifespan by 36 and 29%, respectively, as well as hypersensitivity to heat stress. CHL1 may modulate transcriptional silencing in the presence of Sir proteins [16182251]. | Budding yeast |
| Cisd2 | CDGSH iron sulfur domain 2 | Cisd2 knockouts expire premature ageing and reduced lifespan [19451219]. A persistent level of Cisd2 achieved by transgenic expression extends mean, median and maximum lifespan without any apparent deleterious side effects [22661501]. | House mouse |
| Mcm2 | minichromosome maintenance deficient 2 mitotin (S. cerevisiae) | Conditional knockouts with reduced expression develop normally but lifespan is greatly reduced with most animals living 10-12 weeks accompanied by deficiencies in the proliferative cell compartments of several tissues and increased cancer incidence. | House mouse |
| mir-277 | — | Constitutive miR-277 expression shortens lifespan and synthetically lethal with reduced insulin signaling, indicating that metabolic control underlies this phenotype. Transgenic inhibition with a miRNA sponge construct also shortens lifespan [23669073].
miR-277 is downregulated during adult life [23669073].
mir-277 controls branched-chain amino acid catabolism and as a result it can modulate the activity of TOR kinase [23669073]. | Fruit fly |
| cup-4 | Coelomocyte UPtake defective 4 | cup-4 RNAi or overexpession reduces oxidative stress resistance and shortens lifespan of wild-type under AL. cup-4 RNAi significantly reduces the extended lifespan of eat-2 mutants, but failed to block lifespan extension of age-1 or clk-1 mutants. Lifespan of cup-4 mutants increases only moderately by sDR [19783783]. | Nematode |
| daf-3 | abnormal DAuer Formation | daf-3(mgDf90) mutation decreases mean lifespan by 0-16% and maximum lifespan by up to 9-21%. daf-3(mgDf90) decreases mean lifespan even by 19% [17900898]. Mutation of daf-3 results in a wild-type lifespan, but greatly extends the lifespan of the long-lived daf-9 mutant [11782415]. daf-3 mutations are dauer defective. | Nematode |
| daf-5 | abnormal DAuer Formation | daf-5(e1386) mutation reduces mean lifespan by 19% and maximum lifespan by 21% [17900898]. | Nematode |
| DAP2 | Dipeptidyl AminoPeptidase 2 | DAP2 deletion decreases mean and maximum replicative lifespan under AL by 19 and 36%, respectively, and cancels out the lifespan extending effect of moderate DR [22912585]. | Budding yeast |
| 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 |
| dct-11 | DAF-16/FOXO Controlled, germline Tumor affecting 11 | dct-11 stimulates the growth of gld-1 tumors. RNA interference of dct-11 increases mean lifespan up to 19% in a gld-1 mutant background and reduces mean lifespan by 10% in a wild-type background [17934462]. | Nematode |
| dct-18 | DAF-16/FOXO Controlled, germline Tumor affecting 18 | dct-18 stimulates the growth of gld-1 tumors. RNA interference of dc-18 increases mean lifespan up to 12% in a gld-1 mutant background and reduces mean lifespan by 8% in wild-type worms [17934462]. | Nematode |
| Sirt2 | — | Decreased expression of Sirt2 by RNA interference causes lethality during development. Silencing in neurons shortened mean lifespan by 20% [17159295]. | Fruit fly |
| Sirt6 | — | Decreased expression of Sirt6 by RNA interference causes lethality during development. Sirt6 silencing in neurons shortens mean lifespan by 20% [17159295]. | Fruit fly |
| YKU70 | Subunit of the telomeric Ku complex (Yku70p-Yku80p) | Deletion fo YKU70 shortens lifespan, but does not accelerate the normal aging process [10521401]. YKU70 null mutants are defective for non-homologous end-joining [8754818] and for telomeric silencing [9635192]. | Budding yeast |
| RAD52 | RAD51 homolog (RecA homolog, E. coli) (S. cerevisiae) | Deletion in RAD52 causes a 75% reduction in mean replicative lifespan in PSY316 strain [10207108]. Similiar reduction of lifespan occurs in strains W3031-A and W303R [M. Baeberlein, M. McVey, and L. Guarente, unpublished].
RAD51 is required for formation of extrachromosomal rDNA circles [10207108], but not for replication fork pausing nor DNA breakage with the rDNA [10693764]. | Budding yeast |
| ACO1 | ACOnitase 1 | Deletion of ACO1 decreases mean chronological lifespan by 42 - 56% in diploid cells [21447998]. | Budding yeast |
| AKR1 | AnKyrin Repeat-containing protein 1 | Deletion of AKR1 decreases replicative lifespan by 40% in the alpha strain [18340043]. Replicative lifespan decreased by 50% in the alpha strain [19030232]. | Budding yeast |
| ANS1 | — | Deletion of ANS1 decreases replicative lifespan by 25% in the alpha strain [19030232]. | Budding yeast |
| ARP1 | Actin-Related Protein 1 | Deletion of ARP1 decreases replicative lifespan by 40% in the alpha strain [18340043; 19030232]. | Budding yeast |
| ATP1 | ATP synthase 1 | Deletion of ATP1 increases chronological lifespan by up to 50% [17492370], but decreases replicative lifespan by 70% in the alpha strain [18340043]. | Budding yeast |
| Atr | Ataxia telangiectasia and Rad3 related | Deletion of Atr in young adults eliminates 80-90% of proliferating cells and results in several age-related phenotypes accompanied by a depletion of stem and progenitor cells and exhaustion of tissue renewal and homeostatic capacity [18371340].
Atr mutant mice (so called Seckle mice) exhibit high levels of replicative stress during embryogenesis, when proliferation is widespread, but this is reduced to marginal amounts in postnatal life. In spite of this decrease, adult Seckel mice display accelerated aging, which is further aggravated in the absence of p53. Seckel mice die in less than half a year, exhibit pancytopenia, cachexia and signs of premature aging, including hair graying, kyphosis, osteoporosis, accumulation of fat in the bone marrow, decreased density of hair follicles and thinner epidermis [19620979]. | House mouse |
| BNA6 | Biosynthesis of Nicotinic Acid 6 | Deletion of BNA6 (alias QPT1) has no effect on replicative lifespan and is not required for lifespan extension by DR, but is lethal with mutation of NPT1 [11000115]. Deletion of BNA6 decreases chronological lifespan [17110466]. | Nematode |
| Brca1 | Breast cancer 1 | Deletion of Brca1 causes senescence in mutant embryos and cultured cells and tumorigenesis and signs of premature aging in adults [12533509]. Brca1 heterozygous appear to have shortened lifespan with 70% of tumor incidence. Lymphoma, but not ovarian and mammary gland tumors, occurs commonly in these animals. After a whole-body exposure to ionizing radiation, Brca1 heterozygous mice have a 3-5-fold higher incidence to ovarian tumors, but not lymphoma, when compared with Brca1(+/+) mice [17420720]. | House mouse |
| CAT5 | CATabolite repression 5 | Deletion of CAT5 decreases chronological lifespan by up to 50% [17492370] and also decreases replicative lifespan by 30% in the alpha strain [18340043]. | Budding yeast |
