| C07A9.2 | — | RNA interference of C07A9.2 decreases median lifespan by 26% in wild type animals, 37% in a daf-2 background and 15% in daf-2/daf-16 double mutants [18006689]. | Nematode |
| C11H1.3 | — | RNA interference of C11H1.3 decreases median lifespan by 10% in wild type animals, 14% in a daf-2 background and 41% in daf-2/daf-16 double mutants [18006689]. | Nematode |
| C14A4.9 | — | RNA interference of C14A4.9 decreases median lifespan by 14% in wild type animals and 41% in daf-2 mutants [18006689]. | Nematode |
| C26B9.3 | — | RNA interference ofC26B0.3 decreases median lifespan by 12% in wild type animals, 68% in a daf-2 background and 17% in daf-2/daf-16 double mutants [18006689]. | Nematode |
| C29F9.2 | — | RNA interference of C29F9.2 decreases median lifespan by 12% in wild type animals and 36% in daf-2 mutants [18006689]. | Nematode |
| C33H5.18 | — | RNA interference of C33H5.18 decreases median lifespan by 44% in wild type animals, 77% in a daf-2 background and 14% in daf-2/daf-16 double mutants [18006689]. | Nematode |
| MPT5 | — | Overexpression of MPT5 from the ADH promoter extends replicative lifespan by about 20% in W303R [11805047] and by 25% in PSY142 [9150138], whereas the deletion of MPT5 shortens lifespan by about 50% [9150138; 7859289]. MPT5 deletion decreases average chronological lifespan by 50%, which is rescued to the wild-type level by PKC1 overexpression [17172436].
MPT5 mutants are temperature sensitive [7845352], hypersensitive to mating pheromone [9154842], and null mutants exhibit increased silencing at telomeres and decreased rDNA silencing [9584615]. Deletion of MPT5 is synthetical lethal with mutation of either SWI4, SWI6, or CCR4 in an ssd1-d background [11805047]. MPT5 overexpression suppresses the temperature phenotype of POP2 mutant [9504907]. MPT5 is required for relocalization of the SIR complex to the nucleolus in sir4-42 strain [7859289]. | Budding yeast |
| YIA6 | — | Deletion of YIA6 decreases replicative lifespan by 30% in the a strain [18340043]. | Budding yeast |
| YOL092W | — | Deletion of YOL092W decreases mean and maximum replicative lifespan by 36 and 21%, respectively. Lifespan of YOL092Y deletion mutants is extended by 0.5% glucose restriction [22912585]. | Budding yeast |
| Wrn | — | Mice lacking the helicase domain of the WRN ortholog exhibit many phenotypic features of Werner Syndrom, including a pro-oxidant status and a shorter mean lifespan. Mice with a deletion in the helicase domain [9789047] recapitulates most of the Werner syndrome phenotypes, including an abnormal hyaluronic acid excretion, higher reactive oxygen species levels, dyslipidemia, increased genomic instability, and cancer incidence. Wrn(Dehl/Dehl) mutant mice have a 10 - 15% decrease in their mean lifespan [12707040; 19741171]. | House mouse |
| 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 |
| mir-58 | — | mir-58(n4640) mutation decreases the 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 |
| 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-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 |
| p53 | — | Overexpression of wild-type p53 during adult life has no significant effect on lifespan. Expression of dominant-negative versions of p53 in adult neurons extends lifespan by 58% in females and by 32% in males and increases resistance to genotoxic stress and resistance to oxidative stress, but not to starvation or heat stress, while not affecting egg production or physical activity.
Dominant negative p53 expression cancels out lifespan extension effect of DR, low calorie-food (5% SY). Muscle or fat body specific expression of a dominant negative form of p53 as well as globally lack of p53 decreases lifespan [16303568]. Loss of p53 activity slightly shortens the lifespan. Mutants that lack p53 survive well up to 50 days, but mortality rate increases relative to wild-type at later ages. p53 mutant animals are extremely sensitive to irradiation [12935877].
Expression of dominant-negative (DN) form of p53 in adult neurons, but not in muscle or fat body cells, extends median lifespan by 19% and maximum lifespan by 8%. The lifespan of dietary-restricted flies is not further extended by simultaneously expressing DN-DMp53 in the nervous system, indicating that a decrease in Dmp53 activity may be part of the DR lifespan-extending effect. Selective expression of DN-Dmp53 in only the 14 insulin-producing cell (IPCs) in the brain extends lifespan to the same extent as expression in all neurons and this lifespan extension is not additive with DR [17686972].
| 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 |
| 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 |
| kermit | — | The disruption of kermit (alias dGIPC) function results in premature loss of locomotor activity and reduced mean lifespan [21029723]. | Fruit fly |
| Thor | — | Null mutation in Thor (alias d4E-BP) causes a significant decrease in longevity (-25% median lifespan in males). Thor is strongly upregulated during starvation. foxo and Thor null mutants are compromised in stress resistant. Stress resistance of foxo null mutants is rescued by Thor overexpression [16055649]. Thor is upregulated on the protein level in a foxo-independent manner upon DR, while it is transcriptional induced in a foxo-dependent fashion by starvation. Thor null mutants cancel out DR-induced lifespan extension, because mutants exhibit a diminished change in lifespan when nutrient conditions were varied. Ubiquitously expression of Thor rescued DR response in females and males. Thor null mutants have a wild-type similar reduction in egg production upon DR. Ubiquitously overexpression of wild-type Thor causes no change under AL, but an activated allele (with more than 3-fold increased binding activity to delF4E) significantly extends lifespan of females (weak allele) and females as well as males (strong allele). Mean lifespan is extended by 11 to 40%. Median lifespan of males and females is enhanced by by 11 and 22%, respectively. Maximum lifespan is extended by 16 and 18% for males and females, respectively. Under DR (0.25% YE) there is no lifespan extension, beyond the effect of DR alone, in all (wild-type, weak and strong) Thor alleles [19804760].
Lifespan of animals with increased Pten and 4E-BP activity in muscle exhibit and extended mean and maximum lifespan by 20% and 15.8% [21111239]. | Fruit fly |
| yata | — | yata mutation shortens the maximum lifespan by 68% and results in progressive deterioration of the nervous tissues and aberrant accumulation of Sec23 [19209226]. | 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 |
| ISC1 | Inositol phosphoSphingolipid phospholipase C 1 | ISC1 deletion decreases chronological lifespan [21707788; 21707788]. CTA1
overexpression partially suppresses the shortened lifespan by ISC1. Deletion of SIT4 totally rescues the short lifespan of ISC1 mutants [21707788]. HOG1 deletion partially suppresses the premature aging phenotype and short lifespan of ISC1 deletion [22445853]. | Budding yeast |
