|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 . ||Fly ||— ||— ||— |
|Sod mutation ||Sod mutant flies display infertility and a reduction in lifespan . ||Fly ||— ||— ||— |
|sun mutation ||sun mutations increases lifespan and resistance to oxidative stress  ||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 . ||Fly ||— ||— ||— |
|Surf1 knockdown ||Surf1 knockdown results in larval lethality. However, knockdown in the central nervous system (CNS) not only bypasses the larval lethality but it results in an increase in maximum lifespan of about 20-30% . ||Fly ||— ||— ||+20 to +30 |
|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 . ||Fly ||— ||— ||— |
|UCP2 overexpression ||Overexpression of human UCP2 in the fly nervous system extends lifespan by 10-30%. Ubiquitous overexpression is lethal . ||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 . ||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 . ||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 .
||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 . ||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 . ||Fly ||— ||— ||— |
|alpha-Man-I mutation ||alpha-Man-I mutant fly exhibit enhanced resistance to paraquat and starvation an a 60% increase in mean lifespan for both sexes. After outcrossing, the mutant exhibit, under normal conditions, an increase in mean lifespan of 22% for females and 38% for males. Maximum lifespan is increased by 15% . ||Fly ||+22 to +60 ||— ||+15 |
|alpha-Man-I RNAi ||alpha-Man-I RNAi knockdown results in a 39% increase in mean lifespan . ||Fly ||+39 ||— ||— |
|Atg2 overexpression ||Atg2 overexpression increases average female lifespan by 28% . ||Fly ||+28 ||— ||— |
|Akt1 mutation ||Akt1 homozygotous have a significantly decreased lifespan .
Heterozygous Akt1 animals form dwarfs . ||Fly ||— ||— ||— |
|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 |
|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 . ||Fly ||-28 ||— ||— |
|Atg8a mutation ||Mutations in Atg8a results in reduced lifespan and increased sensitivity to oxidative stress .
Atg8a mutation reduces the maximum lifespan by 25% under starvation conditions .
Loss-of-function mutation in atg8a reduces mean lifespan by 11 - 25% and maximum lifespan by 3 - 22% . ||Fly ||-11 to -25 ||— ||-3 to -25 |
|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 . ||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 . ||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% . ||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 . ||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 . ||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 . ||Fly ||+4 to +46 ||— ||— |