| Pou1f1 knockout | Snell dwarf mutation (Pit1dw) due to knockout of Pou1f1 results in a dramatic lifespan extension. The mean, median and maximum lifespan is increased by 40-50% for Snell dwarf (Pit1dw/Pit1dw) DW/J females, and 25-50% for dwarf DWC3F1 males and females with a compound heterozygous Pit1dw/Pit1dw-J genotype. Although, Snell dwarf (Pit1dw/Pit1dw) DW/J males exhibit aspects of delayed senescence, their median lifespan is by about 25% shorter, probably due to the affects of housing conditions [11718806]. Mice homozygous for loss-of-function mutations at Pit1 locus have a mean and maximum lifespan extension over 40%. Mutant dwJ/dw animals exhibit delays in age-dependent collagen cross-linking and in six age-senstive indices of immune system status. Pituitary transplantation into dwarf mice does not reverse the lifespan extension effect. Male Snell dwarf mice become obese and exhibit proportionately high leptin levels in old age [11371619]. | Mouse | +25 to +50 | +25 to +50 | +25 to +50 |
| RPL10 deletion | Heterozygosity for RPL10 deletion increases median replicative lifespan by 24% [17174052]. | Yeast | — | +24 | — |
| Efemp1 knockout | Efemp1 knockout mice exhibited an early onset of aging-associated phenotypes including a 20% shorted median lifespan and 30% shorter maximum lifespan, decreased body mass, lordokyphosis, reduced hair growth, and atrophy [17872905]. | Mouse | — | +20 | +30 |
| IDH2 deletion | Deletion of IDH2 increases the mean replicative lifespan by about 30% [16293764]. IDH2 deletion extends mean replicative lifespan by 20% in the alpha strain and in a strain [19030232; 18340043]. IDH2 deletion extends mean, median and maximum lifespan by 15, 19 and 15% [23167605]. | Yeast | +15.4 to +30 | +19.2 | +15.4 |
| p53 dominant negative overexpression | 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 Dmp53 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 Dmp53 as well as globally lack of Dmp53 decreases lifespan [16303568].
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].
| Fly | +32 to +58 | +19 | +8 |
| Ctf1 knockout | Absence of Ctf1 is associated with decreased arterial fibrosis, stiffness mad senescence and increased longevity. Ctf1-null mice have a decrease in arterial stiffness and decrease in levels of inflammatory, apoptotic and senescence, whereas telomere-linked and DNA repair proteins as well as antioxidant enzyme activities are increased. The median lifespan of Ctf1-null mice is increased by 5 month (18%) [23172930].
Wild-type and Ctf1-null mice exhibit an increase of senescence markers (p53, Mdm2, p21, and p16) with age but are lower in Ctf1-null mice. Ctf1-null mice have a diminished vascular NFκB signaling, lower inflammation and oxidative stress and reduced senescence. Ctf1-null mice have a 12% increase in body weight, 130% increased adiponectin levels and 51% decreased leptin concentrations [23172930]. | Mouse | — | +18 | — |
| TOR1 Deletion | TOR1 deletion extends mean and maximum replicative lifespan by 21 and 25% [16293764] as well as chronological lifespan [21076178]. This lifespan extension is independent of SIR2 and additive with deletion of FOB1 [16293764]. Deletion of TOR1 fails to increase the replicative lifespan of a sir2 mutant [20947565]. Deletion of TOR1 substantially extends chronological lifespan, increasing median survival almost 3-fold (wild-type 4.5 days, tor1 null 12 days), i.e. by 167%. By 21 days in culture, the vast majority of wild-type cells had died (>99.9%), whereas many tor1 null cells remained viable. Deletion of TOR1 also extends the chronological lifespan of the relatively short-lived BY4742 strain, one of the two haploid genetic backgrounds of the widely used Yeast Knockout Collection available from Open Biosystems. Deletion of TOR1 fails to extend chronological lifespan in Petite strains that are unable to respire [17403371]. TOR1 deletion increases replicative lifespan by 30% in the alpha strain and 20% in a strain [19030232]. TOR1 deletion mutant have and increased mean and maximum replicative lifespan by 21% and 6%, respectively [21931558]. Deletion of TOR1 extends replicative lifespan as well as chronological lifespan [21076178] and glucose restriction fails to further extend the long replicative lifespan of tor1Delta [16293764; 16418483; 18225956]. Water starvation (extreme DR) further extends chronological lifespan of tor1 mutants [18225956]. | Yeast | +21 to +30 | +167 | +6 to +25 |
| TMA19 deletion | Deletion of TMA19 increases median replicative lifespan by 16% (P<0.02) [16806052]. TMA19 deletion increases mean replicative lifespan by 25-30% in the alpha and a strains [19030232]. | Yeast | +25 to +30 | +16 | — |
| Heterozyogous fat-specific Insr knockout (FIRKO) | Deletion of Insr specifically in adipose tissue results in a 15-18% increase in mean, median and maximum lifespan. Fat-specific insulin-receptor knockout (FIRKO) reduces fat mass and protects against age-related obesity and its subsequent metabolic abnormality, without an decrease in food intake. Both male and female FIRKO mice have an increase in mean lifespan of around 134 days (18%), with parallel increases in median and maximum lifespan. FIRKO mice consume the same amount of food on per animal basis as control littermates, but have 15-25% lower body-mass and 50-70% reduced fat mass [12543978]. Disruption of Insr in all tissues reults in neonatal lethality [8612577]. | Mouse | +15 to +18 | +15 to +18 | +15 to +18 |
| Dominant negative Tor | Expression of a dominant-negative form of Tor extends lifespan [15186745]. Ubiquitious overexpression of dTOR with the da-GAL4 driver of UAS-dTOR(FRB) which contains the 11kDA FKB12-rapamycin binding domain led to a mean and maximum lifespan increase of 15% (24%) and 29% at 29°C and of 50% (26%) and 13% at 25°C, respectively [15186745].
Overexpression of the dominant-negative form of Tor specifically in the fat and muscle tissues is sufficient to extend the mean and maximum lifespan by 24 and 19%, respectively [15186745].
Overexpression of UAS-dTOR(WT) or UAS-dTOR(TED) prevents eclosion to adulthood [15186745]. | Fly | +15 to +50 | +13 to +29 | — |
| Ablation of median neurosecretary cells | Flies with an ablation of median neurosecretary cells (which eliminates Ilp2 expression) exhibit a significant increase in mean and maximum lifespan over that of control flies and an increase to oxidative stress and starvation. The mutants also exhibit increased storage of lipid and carbohydrate, reduced fecundity, and reduced tolerance of heat and cold [15708981]. The median and maximum lifespan of females is increased by 33.5% and 40%, respectively. In males the median and maximum lifespan is increased by 10.5% and 27%, respectively [15708981]. | Fly | — | +10.5 to +33.5 | +27 to +40 |
| Prkar2b knockout | Loss of function of Prkar2b results in mice that are lean and insulin sensitive. Both median and maximum lifespan is increased by 14%. Median lifespan is increasesd (from 884 to 1005) and 80% lifespan increased from 941 to 1073 days. There is no difference either in median or 80% lifespan in female genotypes [19536287]. | Mouse | — | +0 to +14 | +0 to +14 |
| ATP2 Deletion | ATP2 deletion decreases replicative lifespan by 50% in the alpha strain [18340043]. | Yeast | — | — | — |
| ATP2 Mutation | A temperature sensitive allele of ATP2 causes a clonal senescence phenotype resulting from the disruption of the age asymmetry between mother and daughter cells in that that daughter cells are born as old as they mother cells at 36 degree Celsius. This Mutation of valine to isoleucine at amino acid 90 does not affect growth on non-fermentable carbon source. This allele is associated with loss of mitochondrial membrane potential as well as failure to segregate functional mitochondria to daughter cells [12242224]. | Worm | — | — | — |
| daf-11 mutation | Lifespan of daf-11(m84) mutant is not significant different from wild type [8247153]. | Worm | — | — | — |
| daf-7 mutation | daf-7 mutation does not significantly change lifespan [8247153]. Mutations in daf-7 cause up to 50% mean and maximum life-extension. This effect is dependent upon daf-3 and on daf-16 but independent of daf-2. daf-7(e1372) increases mean and maximum lifespan by 13-39% and 55%, respectively. daf-7(m62) increases mean and maximum lifespan by 20-29% and 29% [17900898]. | Worm | +13 to +39 | — | +29 to +55 |
| bra-1 mutation | bra-1(nk1) mutation reduces mean lifespan by 6-25% [17900898]. | Worm | -6 to -25 | — | — |
| daf-8 mutation | daf-8 mutation in adults increases mean lifespan by 9-31% but it did not increase maximum lifespan [17900898]. | Worm | +9 to +31 | — | — |
| daf-14 mutation | daf-14(m77) mutation increases mean lifespan by 21-44% and maximum lifespan by 29% [17900898]. | Worm | +21 to +44 | — | +29 |
| daf-5 mutation | daf-5(e1386) mutation reduces mean lifespan by 19% and maximum lifespan by 21% [17900898]. | Worm | -19 | — | -21 |
| kri-1 mutation | kri-1(ok1251) mutation does not shorten the lifespan significantly [22560223]. | Worm | — | — | — |
| rsks-1 mutation | rsks-1 deletion mutants also live longer. TOR RNA interference further extends lifespan of rsks-1 mutants [17266679]. | Worm | — | — | — |
| rrf-1 mutation | Although rrf-1(pk1417) mutants seem to have elevated DAF-16 activity (as sod-3 transcript level is increased) the mean and maximum lifespan or ability to withstand elevated temperature is not different from wild-type [22574120]. | Worm | — | — | — |
| bar-1 mutation | BAR-1 may play a role in regulating daf-16 during dauer formation, particularly in conditions of oxidative stress as it directly interaction with DAF-16 and loss of bar-1 reduces activity of DAF-16 in dauer formation and lifespan. Deletion of bar-1 reduces mean (44%) and maximal (18%) lifespan, which is to a similar degree as seen to daf-16 mutants [15905404]. | Worm | -44 | — | -18 |
| hcf-1 mutation | hcf-1 inactivation by mutation cause a daf-16-dependent lifespan extension of up to 40% and heightened resistance to specific stimuli [18828672].
HCF-1 forms a complex with DAF-16. hcf-1 inactivation by mutation cause a daf-16-dependent lifespan extension of up to 40% and heightened resistance to specific stimuli. The hcf-1(ok559) mutation increases mean and maximum lifespan by 10-37 and 29%, while the strong hcf-1(pk924) mutation extends mean and maximum lifespan by 29-31 and 53-88%, respectively. In the absence of hcf-1 there is a greater enrichment of DAF-16 at its target gene promoters and more robust DAF-16-mediated regulation of selective transcriptional targets. hcf-1 mutation extends lifespan of glp-1(e2141) mutants which lack germline cells, [18828672]. | Worm | +10 to +37 | — | +29 to +88 |
GenAge
GenDR
