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 | — | — | — |
Sod mutation | Sod mutant flies display infertility and a reduction in lifespan [2539600]. | Fly | — | — | — |
Akh overexpression | Overexpression of Akh in a ubiquitousness manner enhances fat metabolism (significant increase in triglyceride synthesis and breakdown under AL), spontaneous activity (148% on AL and 154% on DR), and lifespan on AL (33%). However, despite and increase in movement under DR, lifespan is not increased under a restricted diet [22768842]. | Fly | — | +33 | — |
sun mutation | sun mutations increases lifespan and resistance to oxidative stress [15133470] | 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 | — | — | — |
UCP2 overexpression | Overexpression of human UCP2 in the fly nervous system extends lifespan by 10-30%. Ubiquitous overexpression is lethal [16054055]. | Fly | +10 to +30 | — | — |
rpr overexpression | Flies with ablated wings caused by overexpressing reaper (UAS-rpr) with a wing-specific Gal4 enhancer trap (1096-Gal4) exhibit only a 14% extension in lifespan compared to controls which exhibit a 61% extension upon DR [22768842]. | Fly | — | — | — |
14-3-3epsilon mutation | Loss of 14-3-3ε results in increased stress-induced apoptosis, growth repression and extended lifespan of flies, in a foxo-dependent manner. Mean lifespan of males and females is increased by 25% and 49%, respectively. Increased 14-3-3ε expression also reverts foxo-induced growth defects. No effect of lifespan is observed when overexpressing 14-3-3ε in adipose tissue, indicating that endogenous foxo activity in this tissue is low under normal conditions [18665908]. | Fly | +25 to +49 | — | — |
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 | — | — | — |
Akt1 RNAi | RNA interference of Akt1 in intestinal stem cells, results in impaired regeneration of the intestinal epithelium and a short lifespan. In males and females on mean lifespan is 11.4% and 7.4% lower [20976250]. | Fly | -11.4 to -7.4 | — | — |
Single-housing | Single-housed male flies that are restricted in small activity tubes exhibit significant increase in lifespan on a sugar-based DR regimen [22570630]. | Fly | — | — | — |
alpha-Man-I RNAi | alpha-Man-I RNAi knockdown results in a 39% increase in mean lifespan [19302370]. | Fly | +39 | — | — |
Atg2 overexpression | Atg2 overexpression increases average female lifespan by 28% [18059160]. | Fly | +28 | — | — |
Akt1 mutation | Akt1 homozygotous have a significantly decreased lifespan [11292874].
Heterozygous Akt1 animals form dwarfs [11292874]. | Fly | — | — | — |
Aut1 RNAi | Aut1 depletion by RNAi form the first day of imaginal stage shortens lifespan by 28% on average in Drosophila and causes morphological behavioural features of premature aging [18219227]. | Fly | -28 | — | — |
Bam mutation | Bam mutants have an extended lifespan due to germ cell loss. Lifespan of females is on average up to 50% higher and that of males on average s up to 27.8% higher [18434551]. | Fly | +27.8 to +50 | — | — |
Atg8a overexpression | Enhanced expression of Atg8a in older fly brains extends average adult lifespan by 56% and promotes resistance to oxidative stress [18059160]. | Fly | +56 | — | — |
bsk RNAi | RNA interference of bsk in intestinal stem cells, results in short lived mutants with impaired intestinal homeostasis and tissue regeneration. The mean lifespan of males is 16.4% lower and those of female is reduced by 10.2% [20976250]. | Fly | -10.2 to -16.4 | — | — |
CG17856 RNAi | RNAi of CG17856 results in an increase in mean lifespan of 13-18% in females. In the case of males and post-developmental experiments the results are variable [19747824]. | Fly | +13 to +18 | — | — |
CG18809 RNAi | RNAi of CG18809 results in a 7-19% increase in mean lifespan of females, while neural RNAi results in an increased mean lifespan of up to 12% in females. For males the results are variable [19747824]. | Fly | +7 to +19 | — | — |
CG9172 RNAi | RNAi against CG9172 increases mean lifespan in females by up to 4-12% when applied in both development and adulthood, and up to 46% when applied in adult neurons only. For males the effect is variable [19747824]. | Fly | +4 to +46 | — | — |
DNApol-gamma35 overexpression | Overexpression of DNApol-gamma35 (DNA polymerase gamma) in the nervous system results in a decrease in the median lifespan ranging from 39% to 52% [17999718]. | Fly | -39 to -52 | — | — |
dys RNAi | dys RNAi-mediated knockdown in the mesoderm shortens lifespan [18221418]. | Fly | — | — | — |
E(z) mutation | Flies heterozygous for the protein null E(z)63 or the catalytically inactive E(z)731 mutation that are progeny of an out-cross to an Oregon-R (O-R) wild-type strain exhibit a substantially greater median lifespan than the O-R control (71% and 76%, respectively). When derived from an out-cross to a longer-lived Canton-S (C-S) wild-type strain, the median lifespan of E(z)63 heterozygous is 33% longer than the C-S control [20018689]. | Fly | — | +33 to +76 | — |