| Mnt | CG13316-PC, isoform C | A dMnt null allele results in flies with larger cells, increased weight, and decreased lifespan [16055719]. | Fruit fly |
| lin-4 | abnormal cell LINeage 4 | A loss-of-function mutation in lin-4 shortens lifespan and accelerated tissue ageing while overexpressing lin-4 extends lifespan by redarding aging [16373574].
lin-4 is regulated by DAF-16 in L1 arrest. | Nematode |
| Nlaz | Neural Lazarillo | Absence of Nlaz, which is homologous to ApoD, results in a reduced lifespan in both sexes. Median lifespan is 30.8% and 22.5% lower in females and males, respectively. Maximum lifespan is reduced by 12% and 30% in females and males [21376794]. | Fruit fly |
| Aut1 | — | Aut1 depletion form the first day of imaginal stage shortens lifespan by 28% on average in Drosophila and causes morphological behavioural features of premature aging [18219227]. | Fruit fly |
| CG3776 | — | Both overexpression and underexpression of CG3776 (alias Jhebp29) reduces the mean lifespan, where the reduction in males is slightly higher.
The lifespan of male flies with under- and overexpressed CG3776 is reduced by 38.8 and 42.6%, respectively when compared with Oregon R flies.The lifespan of female flies with under- and overexpressed CG3776 is reduced by 31.6 and 35%, respectively when compared to Oregon R flies.
Among the males and females, relatively to Oregon R and EP835/CyO, the age-specific survival of EP835/EP835 and EP835/Gal4 is reduced in both log-rank and Wilcoxon tests (P < 0.001); survival of EP835/EP835 and EP835/Gal4 differed using the log-rank-test (male: P<0.001; female: P=0.027) [18275960].
| Fruit fly |
| 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 |
| 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 |
| 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 |
| SNF4Agamma | SNF4/AMP-activated protein kinase gamma subunit | Deletion of SNF4Agamma from the first day of the imaginal stage shortens mean lifespan by 23% and causes morphological and behavioural features of premature aging [18219227]. | Fruit fly |
| elav | embryonic lethal abnormal vision | elav mutation significantly decreases the lifespan. Median lifespan in males is 66% lower [20589912]. | Fruit fly |
| 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 |
| Sh | Shaker | Genetic mutation in Sh decreases lifespan by accelerating the aging process. At 25 degree mean and maximum lifespan is reduced by 16 and 22%, while by 18 degree Celsius the reduction is 32 and 21% [8582611]. | Fruit fly |
| Pi3K92E | Phosphatidylinositol-3-kinase | Heterozyogous mutation in Pi3K92E fails to extend lifespan [11292874] and it is recessive lethal.
Overexpression of a dominant-negative Pi3K92E (DP110) results in mutants that have impaired regeneration of the intestinal epithelium and are short lived with a reduction of the mean lifespan by 2.8% for males and 5.0% for females [20976250]. | Fruit fly |
| mle | maleless | Homozygous mutant animals (mle napts) display a shortened median lifespan and increased frailty in both males and females [18208580]. | Fruit fly |
| mir-71 | — | Loss and gain-of-function of mir-71 decreases and increases lifespan, respectively [21129974]. mir-71 mutants have a reduced lifespan with 40% decrease in mean lifespan, while extra copies of mir-71 extend the lifespan with an increase in lifespan by 15 - 25% [22482727],
Loss of mir-71 function suppresses the long lifespan of glp-1(e2141) mutants [22482727],
During adulthood mir-71 is strongly expressed in the intestine, body wall muscles and neurons. mir-71 is upregulated in aging adults [22482727], | Nematode |
| Dys | Dystroglycan | Loss of dys function in the heart leads to an age-dependent disruption of the myofibrillar organization within the myocardium as well as to alterations in cardiac performance. dys RNAi-mediated knockdown in the mesoderm also shortens lifespan. Mesodermal dys knockout results in a morderate maximum lifespan reduction (13%), but not when exclusively targeted to the heart. In contrast, half of the transheteozygous DysExel618/Dyskx43 deficiency flies die at 29 days compared to 63 days in controls. This indicates that a moderate dye loss-of-function in all muscles, but not in just the heart, reduces the normal lifespan [18221418]. | Fruit fly |
| mir-124 | — | Loss of mir-124 increases reactive oxygen species formation and accumulation of the aging marker lipofuscin, reduces whole body ATP levels and results in reduction in lifespan [23075628].
Supplementation of vitamin C normalizes the reduced median lifespan of mir-124 mutants [23075628].
The expression of the conserved mir-124 in whole wrn-1 mutants (which premature age) is significantly reduced [23075628]. | Nematode |
| g | garnet | Loss-of-function mutation in g reduces mean lifespan by 11 - 42% and maximum lifespan by 7 - 30% [17435236]. | Fruit fly |
| rb | ruby | Loss-of-function mutation reduces mean lifespan by 33% and maximum lifespan by 22% [17435236]. | Fruit fly |
| mir-58 | — | mir-58(n4640) mutation decreases the mean lifespan by 20% [22482727]. | Nematode |
| mir-14 | mir-14 stem loop | Mutating mir-14 decreases lifespan in both sexes. mir-14 reduces the mean and maximum lifespan of females by 55 and 36%, respectively, while those of males is reduced by 29 and 21%, respectively [12725740].
| Fruit fly |
| mir-238 | — | Mutating mir-238 decreases mean and maximum lifespan by 18 and 24% [21129974]. mir-238(n4112) mutation decreases mean lifespan by 20% [22482727]. | Nematode |
| mir-246 | — | Mutating mir-246 decreases mean and maximum lifespan by 12%, while its overexpression increases mean and maximum lifespan by 6 and 5 - 14%, respectively [21129974]. | Nematode |
| WRN | Werner syndrome, RecQ helicase-like | Mutation in WRN causes Werner Syndrome which characteristics includes prematurely aged facies, scleroderma-like skin changes, cataracts, arteriosclerosis, subcutaneous calcification, and diabetes mellitus [McKusick et al. 1963; 5327241]. Inheritance is autosomal recessive and malignancy is frequent. THe frequency is 3 per million individuals in Japan [7460386].
Cells from a Werner heterozygote exit the cell cycle at a faster rate than do normal cells [8265666]. Loss of WRN promoter aberrant mitotic recombination [11316787].
The single nucleotide polymorphism rs1800392 in WRN has been associated with exceptional longevity in a plethora of genetic signatures [22279548]. WRN was found to be associated with longevity [10069711; 20855428; 20855428; 20855428 ;17903295; 22406557; 16405962; 16405962; 16405962; 20855428; 20855428; 20855428; 22279548]. WRN was found to be associated with longevity [24244950]. | Human |
