Interventions

  • Species: + -
  • name effect species mean median maximum
    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
    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
    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
    alpha-Man-I RNAi alpha-Man-I RNAi knockdown results in a 39% increase in mean lifespan [19302370]. Fly +39
    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
    dys RNAi dys RNAi-mediated knockdown in the mesoderm shortens lifespan [18221418]. Fly
    Mlp84B RNAi RNA interference of Mlp84B specifically in the heart results in bradycardia and heart rythm abnormalities as well as a shorter mean lifespan in males but not in females [18083727]. Fly
    car mutation Loss-of-function mutation in car results in reduction of mean lifespan by 34 - 63% and maximum lifespan by 28 - 29% [17435236]. Fly -34 to -63 -28 to -29
    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
    Sod2 RNAi RNA interference of Sod2 results in increased oxidative stress and early-onset mortality in young adults [12456885]. 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
    Sirt6 RNAi Decreased expression of Sirt6 by RNA interference causes lethality during development. Sirt6 silencing in neurons shortens mean lifespan by 20% [17159295]. Fly -20
    Sir2 knockdown A diet-dependent lifespan phenotype of dSir2 knockdown in the fat-body, but not in muscles, negates the effects of background genetic mutants. dSir2 knockdown abrogates fat-body dFoxo-dependent lifespan extension [23246004]. Fly
    l(3)neo18 RNAi Under rich nutritional conditions lifespan of l(3)neo18 (alias CG9762) RNAi knockout animals is indistinguishable from wild-type, while upon DR, lifespan extension is diminished in males and females [19804760]. Fly
    CG5389 RNAi RNAi of complex V subunit CG5389 results in increased mean longevity under standard laboratory food conditions (3% yeast) in males. RNAi started from the development results in a mild lifespan increase in both sexes (3-11% in females and 3-8% in males). Post-developmental RNAi and silencing limited to neurons has variable effects with reduction in lifespan of up to 9% [19747824]. Under rich media conditions CG5389 knockdown throughout development and adulthood increases mean lifespan by 26% and abolished the lifespan extension by DR (started in the adulthood) in males. Suppression of CG5389 only during the adulthood either via RNAi by tub-GS or via oligomycin (a specific inhibitor of complex V) feeding prevents an increase in longevity under DR (started in the adulthood) in males [19968629]. Fly -9 to +26
    Indy mutation Flies heterozygotic for a disruption in Indy gene have extended mean (87-92%) and maximum (45%) lifespan. Homozygotes for the disruption show only a 10 - 20% increase in mean lifespan [11118146]. Heterozygous insertion of a p-element in the non-coding region of Indy locus leads to a reduction in Indy mRNA expression and causes a significant median lifespan extension in male and female by about 29% and 34%, respectively. At normal or high calorie conditions Indy heterozygote mutants have a significant lifespan extension, but under low calorie conditions, Indy heterozygous mutants have minimal median lifespan extension. Reduction of calorie content from high to normal calorie condition results in 19% decline in Indy mRNA and from normal to low calorie condition results in additional 9% decrease in Indy mRNA. Reduction of calorie content from high to normal calorie conditions in heterozygous Indy mutants leads to 20% reduction in Indy mRNA expression without any additional decrease upon further reduction to low calorie food. Maximum lifespan extension is associated with Indy mRNA levels between 25 - 75% of normal. Long-lived heterozygous Indy mutants on high-calorie food and normal wild-type on low-calorie food have several phenotypes in common: 50 - 60 % reduced mRNA expression levels of Ilp2, Ilp3 and Ilp 5; similar high percentage of anti-FOXO-positive nuclei in fat body cells; higher sensitivity to starvation; do not gain weight; similar decrease in triglycerides and fat storage; normal food intake [19470468]. Mutations in Indy dramatically extend lifespan without a loss in fertility, physical activity, flight velocity or metabolic rate [11118146; 12626742]. Indy encodes a high-affinity dicarboxylate/citrate plasma membrane transporter found most abundantly in adult fat body, oenocytes and midgut cells, the primary sites of intermediary metabolism [12391301]. Indy mutation alters metabolism in a manner similiar to DR and mutants have several phenotypes with long-lived DR files in common, including decreases insulin-like signaling, lipid storage, weight gain, and resistance to starvation, and an increase in spontaneous physical activity [19470468]. Of the Indy206 and Indy302 mutation only one of the two has lower mRNA levels and both do not extend lifespan of female flies in any genetic background. In original genetic background only Indy mutation associated with altered RNA expression extends the lifespan of males. This effect is abolished by back-crossing into standard out-bred genetic backgrounds and is associated with an unidentified locus on the X chromosome. Original Indy line with long-lived males is infected by the cytoplasmic Wolbachia. Longevity of Indy males disappear after tetracycline clearance of this endosymbiont [17571923]. Fly +10 to +92 +45
    Heterozygous hypomorphic Rpd3 mutation Males heterozygous for hypomorphic (partial loss-of-function) mutation of Rpd3 have a lifespan extension of 33%. Females heterozygous for a hypomorphic allele have a 52% increase in lifespan. Longevity increases to the same extent in wild-type under low-calorie diet and rpd3 mutants fed normal diet [12459580]. Fly +33 to 52
    Sirt2 RNAi Decreased expression of Sirt2 by RNA interference causes lethality during development. Silencing in neurons shortened mean lifespan by 20% [17159295]. Fly -20
    Ilp2 RNAi Ilp2 RNA interference results in a 24% to 47% increase in median lifespan [19005568]. Fly +24 to +47
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    • 25 of 26 interventions
    Interventions are an extension of GenAge and GenDR.