| mld heterozygous mutation | Female, but not male, heterozygous mutants display a 42% increase in mean lifespan at 29 degrees Celsius. DTS-3 +/- female adults exhibit a 50% reduced ecdysone titer and reduced fertility [12610309]. Female, but not male, heterozygoutes also exhibit a temperature-dependent increase in starvation resistance. | Fly | +42 | — | — |
| EcR mutation | Mutant heterozygotes in EcR live on mean 40%-50% longer than controls [12610309; reviewed in 12610294]. Homozygous mutants in EcR are inviable. The developmental time and weight of EcR+/- mutants is the same as control, but resistance to temperature, oxidative stress, and starvation is increased in heterozygotes [12610309]. | Fly | +40 to +50 | — | — |
| mth mutation | Mutants in mth display approximately 35% and 36% increase in average and maximum lifespan as well as enhanced resistance to various forms of stress (including starvation, high temperature, and dietary paraquat) [9794765]. | Fly | +35 | — | +36 |
| Hk mutation | Genetic mutation in Hyperkinetic shortens lifespan through acceleration of the aging process. At 25 degree Celsius mean and maximum lifespan is reduced by 29 and 32%, while by 18 degree Celsius the reduction is 59 and 39% [8582611]. | Fly | -29 to -59 | — | -32 to -39 |
| Sh mutation | Genetic mutation in Sh decrease lifespan by accelerating the aging proces. 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]. | Fly | -16 to -32 | — | -21 to -22 |
| GLaz mutation | Loss-of-function mutation of GLaz which decreases its expression of GLaz results in shorter lifespan and decreased resistance to oxidative stress in males [16581513]. | Fly | — | — | — |
| hypomoprhic hep mutation | A hypomorphic allele of hep (hep1) laerlgy prevents lifespan extension caused by puc heterozygosity [14602080]. | Fly | — | — | — |
| InRE19/InRp5545 transheterozygous mutation | Mutations in InR (InRE19/InRp5545 transheterozygous) result in dwarf females with extended lifespan of up to 85% and dwarf males with reduced late age-specific mortality (although no significant change in lifespan) [11292875]. | Fly | +85 | — | — |
| InrGC25/InrE19 transheterozygous mutation | InrGC25/InrE19 transheterozygous animals are short-lived an exhibit an elevated rate of age-independent mortality [11292874]. | Fly | — | — | — |
| ovo mutation | The dominant ovoD1 allele extends female lifespan by approximately 50%. It does not synergize or prevent life-extension caused by chico [10617470; 11292874].
ovoD1 mutants are sterile [Mevel-Ninio et al. 1991]. | Fly | +50 | — | — |
| Akt1 mutation | Akt1 homozygotous have a significantly decreased lifespan [11292874].
Heterozygous Akt1 animals form dwarfs [11292874]. | Fly | — | — | — |
| puc mutation | Heterozygous loss-of-function mutations in puc (either pucA241.1 or pucE69) significantly extend median and maximum lifespan and increase resistance to oxidative stress. Heterzyogosity for puc only modestly extends lifespan in animals carrying a hypomorphic allele of the JNK kinase hep [14602080].
puc heterzyogotes do not differ signficantly from wild-type for body size, reproductive activity or developmental timing, but exhibit increased resistance to oxidative stress and starvation [14602080]. | Fly | — | — | — |
| Sod1 knockdown | Sod1 knockdown by RNAi blunts the lifespan extension by a high sugar-low protein diet, but not a low-calorie diet [22672579]. | Fly | — | — | — |
| Sod knockout | Sod knockout blunts the lifespan extension by a high sugar-low protein diet, but not a low-calorie diet [22672579]. | Fly | — | — | — |
| Sod2 RNAi | RNA interference of Sod2 results in increased oxidative stress and early-onset mortality in young adults [12456885]. | Fly | — | — | — |
| Wings ablation/clipping | Flies on DR who could not move or had inhibited fat metabolism in their muscle and do not get an extended lifespan. Flies with ablated wings caused by overexpressing reaper (UAS-rpr) with a wing-sepcific Gal4 enhancer trap (1096-Gal4) exhibit only a 14% extension in lifespan compared to controls which exhibit a 61% extension upon DR. Clipped wing flies exhibit a modest 33% increase, while controls exhibit a 97% lifespan extension upon DR Lifespan reduction upon DR by curtailing movement is specific to control animals as lifespan is not futher reduced with Akh inhibition [22768842].
Control and clipped-wing flies exhibit a similiar level of fat synthesis and breakdown. Muscle specific RNAi of Akh, CG7834, or CG4389 results in a significant reduction in movement of flies upon DR [22768842]. | Fly | — | — | — |
| Akh knockdown | Knockdown of the adipokinetic hormone (Akh) by RNAi (with an RU486-inducible and ubiquitously expressing Actin 5C-GS Gal4 strain) does not by itself affect lifespan, but significantly inhibits the DR-dependent increase in lifespan across a range of yeast concentrations in both females and males. While control females and males exhibit a 113%/22% increase in lifespan under DR, upon Akh inhibition there was a significant reduction in lifespan extension with DR (52%/5%). Global Akh knockdown reduces starvation resistance by 24% upon DR, but no significant change upon AL. Also Akh RNAi repressed the DR-dependent increase in cold-stress resistance. Fat body and neuronal-specific inhibition of Akh by using RU486-inducible S(1)106-GS-Gal4 and Elav-GS-Gal4 enhancer traps, respectively, does not reduce lifespan extension upon DR. But, muscle-specific inhibition of Akh using RU486-inducible muscle enhancer trap (Mhc-GS-Gal4) reduces the DR-dependent increase in lifespan. While control exhibit a 47.2% lifespan extension, animals with muscle-specific Akh inhibition fails to result in any increase upon DR (i.e. completely blocked the DR lifespan extension). Muscle-specific Akh inhibition diminishes the increase in triglyceride synthesis and breakdown present normally under DR. A significant reduction in lifespan extension also occurs with a noninducible muscle driver (Mhc-Gal4). Controls on DR exhibit significant higher levels of spontaneous activity compared to Akh RNAi-inhibited animals at all ages. Akh inhibition reduces the protective effect of DR on age-related decline in muscle function/activity [22768842]. | Fly | — | — | — |
| CG4389 knockdown | Muscle specific RNAi knockdown of CG489 which reduces its mRNA levels by 25-35%, significantly reduces the DR-dependent lifespan extension. CG4389 RNAi animals exhibit only 20% increase while controls display an lifespan increase by 123% upon DR [22768842]. | Fly | — | — | — |
| CG7834 knockdown | Muscle specific RNAi knockdown of CG7834 which reduces its mRNA levels by 25-35%, significantly reduces the DR-dependent lifespan extension. CG7834 RNAi animals exhibit only a 14% increase compared to the 55% lifespan-increase in controls upon DR [22768842]. | Fly | — | — | — |
| Fat-body specific Akh knockdown | Fat-body specific Akh RNAi results in increased spontaneous activity and a small but significant increase in lifespan upon AL [22768842].
| Fly | — | — | — |
| Ilp3 mutation | Ilp3 null mutants have a normal lifespan under AL and a normal DR response. Ilp2 Ilp3 Ilp5 triple null mutants fail to have a normal response to DR. Their response is right shifted, with mutants being shorter-lived compared to wild-type on low but longer-lived on high yeast concentrations [20195512]. | Fly | — | — | — |
| Ilp5 mutation | Abundance of Ilp5 mRNA is reduced under DR. Ilp5 null mutants have a normal lifespan under AL and a normal DR response. Ilp2 Ilp3 Ilp5 triple null mutants fail to have a normal response to DR. Their response is right shifted, with mutants being shorter-lived compared to wild-type on low but longer-lived on high yeast concentrations [20195512]. | Fly | — | — | — |
| Cbs RNAi | Cbs RNAi partially abrogates increased lifespan by DR, but has no effect on fully fed animals. Cbs upregulation is required for increased lifespan under low-nutrient conditions. Response of male flies to DR is muted in comparison with females [21930912]. | Fly | — | — | — |
| Igf1 overexpression | Cardiac specific overexpression of Igf1 results in a 23% increase in median lifespan, though no increase in maximum lifespan [17973971]. | Fly | — | +23 | — |
| Atg7 knockout | Knockouts of Atg7 are short-lived with a 30% reduction in maximum lifespan and are hypersensitive to nutrient and oxidative stress [18056421; 19550147]. | Fly | — | — | -30 |
GenAge
GenDR
