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 | — | — | — |
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% [16172499]. | 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 [22768842]. | Fly | — | — | — |
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 | — | — | — |
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 | — | — | — |
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 | — | — | — |
Akt1 mutation | Akt1 homozygotous have a significantly decreased lifespan [11292874].
Heterozygous Akt1 animals form dwarfs [11292874]. | 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 |
dys knockout | Loss of dys function in the heart leads to an age-dependent disruption of the myofibrillar organization within the myocardium as well as to alterations in cardiac performance. Mesodermal dys knockout results in a morderate maximum lifespan reduction (13%), but not when exclusively targeted to the heart. In contrast, half of the transheteozygous DysExel618/Dyskx43 deficiency flies die at 29 days compared to 63 days in controls. This indicates that a moderate dye loss-of-function in all muscles, but not in just the heart, reduces the normal lifespan [18221418]. | Fly | — | — | -13 |
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 | — |
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 | — | — | — |
DHEA treatment | DHEA treatment increases the lifespan of female fruit flies [Li et al., 2000]. | Fly | — | — | — |
elav mutation | elav mutation significantly decreases the lifespan. Median lifespan in males is 66% lower [20589912]. | Fly | — | — | — |
fh overexpression | Overexpression of fh in the mitochondria of female transgenic animals increases antioxidant capability, resistance to oxidative stress insults, and longevity [18258192]. | Fly | — | — | — |
Gr63a overexpression | Overexpression of Gr63a has modest negative effect on lifespan [20422037]. | Fly | — | — | — |
Hsp22-promoter driven reporter overexpression | Hsp22-promoter driven reporter overexpression reduces mean and maximum lifespan [19420297]. | Fly | — | — | — |
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 |
aPKC transposition | Insertion of a P-based vectors in the structural part of aPKC increase male and female lifespan [22661237]. | Fly | — | — | — |
Ilp2 RNAi | Ilp2 RNA interference results in a 24% to 47% increase in median lifespan [19005568]. | Fly | — | +24 to +47 | — |
Gadd45 overexpression | Gadd45 overexpression in the nervous system leads to a significant increase of lifespan without a decrease in fecundity and locomotor activity. The lifespan extension effect is more pronounced in males than in females. Additional maximum lifespan is also extended. The maximum lifespan is increased by 50% and 59% for females and males, respectively. The median lifespan is extended by 46 and 77% for females and males, respectively [22661237]. | Fly | — | — | — |