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 | — | — | — |
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 | — |
AKR1 deletion | Deletion of AKR1 decreases replicative lifespan by 40% in the alpha strain [18340043]. Replicative lifespan decreased by 50% in the alpha strain [19030232]. | Yeast | -40 to -50 | — | — |
akt-1 RNAi | RNA interference of akt-1 leads to lifespan extension [15998808]. | Worm | — | — | — |
Akt1 mutation | Akt1 homozygotous have a significantly decreased lifespan [11292874].
Heterozygous Akt1 animals form dwarfs [11292874]. | 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 | — | — |
alg-1 RNAi | Adult-specific knockdown of the C. elegans argonaute-like gene 1 *alg-1* results in shortened lifespan with a reduction in the mean and maximum lifespan by 9 - 16% and 14%, respectively [21810936]. | Worm | -9.6 to -16.1 | — | -13.7 |
alg-2 RNAi | RNA interference of alg-2 decreases median lifespan by 24% in wild type animals and 50% in a daf-2 background [18006689]. | Worm | — | -24 | — |
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% [19302370]. | Fly | +22 to +60 | — | +15 |
alpha-Man-I RNAi | alpha-Man-I RNAi knockdown results in a 39% increase in mean lifespan [19302370]. | Fly | +39 | — | — |
amt-2 RNAi | RNA interference of amt-2 increases mean lifespan by 20% [17608836]. | Worm | -20 | — | — |
ANS1 deletion | Deletion of ANS1 decreases replicative lifespan by 25% in the alpha strain [19030232]. | Yeast | -25 | — | — |
ant-1.1 RNAi | RNA interference of ant-1.1 increases mean lifespan by 40% [17608836]. | Worm | +40 | — | — |
APD1 deletion | Although APD1 was identified as a potential long-lived mutant strain in a bar-code screen, deletion of APD1 does not significantly affect chronological lifespan under starvation/extreme DR [20657825]. | Yeast | — | — | — |
aph-2 RNAi | aph-2 RNAi in the adulthood extends the lifespan [New longevity regulators]. | Worm | — | — | — |
aPKC transposition | Insertion of a P-based vectors in the structural part of aPKC increase male and female lifespan [22661237]. | Fly | — | — | — |
Apple polyphenol supplementation | Supplemention of the diet with apple polyphenol significantly extends mean lifespan by 10% and is accompanied by up-regulation of SOD1, SOD2 and CAT as well as downregulation of MTH in aged animals [21319854]. | Fly | +10 | — | — |
Apply polyphenol treatment | Treatment with 100 microgram/mL apple polyphenol increases mean lifespan of wild-type N2 and FEM-1 by 12.0 and 5.3%, respectively [20717869]. | Worm | +5.3 to 12.0 | — | — |
apr-1 RNAi | apr-1 RNAi in the adulthood extends the lifespan [99999999]. | Worm | — | — | — |
aps-1 RNAi | aps-1 RNAi in the adulthood extends mean lifespan by 8% without any apparent effect on maximum lifespan [23144747]. | Worm | +7.9 | — | 0 |
aqp-1 mutation | Similar to daf-16 and hsf-1 mutants, aqp-1 mutants were short-lived, and their short lifespan was not further decreased by glucose. Overexpression of aqp-1::GFP rescued short lifespan of aqp-1 deletion mutants and partially prevented glucose from shortening lifespan. aqp-1 mutation does not further decrease the short lifespan of daf-16 and/or hsf-1 mutants. Dietary glucose does not cause significant differences in levels of glucose or glycerol in wild-type vs. aqp-1 mutants [19883616]. | Worm | — | — | — |
aqp-1 overexpression | Overexpression of aqp-1::GFP rescues short lifespan of aqp-1 deletion mutants and partially prevented glucose from shortening lifespan. | Worm | — | — | — |
arf-3 RNA | RNA interference of arf-3 does not affect lifespan of wild-type but suppresses lifespan extension by isp-1 mutation [22829775]. | Worm | 0 | — | — |
Arhgap1 knockout | Most Ahrgap1 knockout mice are weak and die during the neonatal period. Animals that survived have a shorter lifespan (median lifespan is 12 months) and show premature aging-like phenotypes, including a reduction in body mass, a loss of subdermal adipose tissue, lordokyphosis, and osteoporosis [17227869]. | Mouse | — | — | — |
arl-8 RNAi | RNA interference of arl-8 decreases median lifespan by 35% in a daf-2 background and 9% in daf-2/daf-16 double mutants [18006689]. | Worm | — | -35 | — |