| Nlaz | Neural Lazarillo | Absence of Nlaz, which is homologous to ApoD, results in a reduced lifespan in both sexes. Median lifespan is 30.8% and 22.5% lower in females and males, respectively. Maximum lifespan is reduced by 12% and 30% in females and males [21376794]. | Fruit fly |
| hebe | — | Adult-specific overexpression of hebe increases the lifespan by 5-30% and modulates late-age female fecundity. Female and male mean lifespan is up to 11% and 24% higher [19011900]. | Fruit fly |
| magu | — | Adult-specific overexpression of magu increases lifespan by 5-30% and modulates late-age fecundity [19011900]. | Fruit fly |
| Atg2 | Autophagy-specific gene 2 | Atg2 overexpression increases average female lifespan by 28% [18059160]. | Fruit fly |
| Aut1 | — | Aut1 depletion form the first day of imaginal stage shortens lifespan by 28% on average in Drosophila and causes morphological behavioural features of premature aging [18219227]. | Fruit fly |
| bam | bag of marbles | 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]. | Fruit fly |
| CG3776 | — | Both overexpression and underexpression of CG3776 (alias Jhebp29) reduces the mean lifespan, where the reduction in males is slightly higher.
The lifespan of male flies with under- and overexpressed CG3776 is reduced by 38.8 and 42.6%, respectively when compared with Oregon R flies.The lifespan of female flies with under- and overexpressed CG3776 is reduced by 31.6 and 35%, respectively when compared to Oregon R flies.
Among the males and females, relatively to Oregon R and EP835/CyO, the age-specific survival of EP835/EP835 and EP835/Gal4 is reduced in both log-rank and Wilcoxon tests (P < 0.001); survival of EP835/EP835 and EP835/Gal4 differed using the log-rank-test (male: P<0.001; female: P=0.027) [18275960].
| Fruit fly |
| Cdk5 | Cyclin-dependent kinase 5 | Cdk5 loss-of-function mutations result in defective axon guidance, age-dependent behavioral deficits and reduced lifespan by about one third [17368005]. | Fruit fly |
| cert | ceramide transfer protein | cert mutants exhibit a shortened lifespan accompanied by enhanced oxidative damage to cellular proteins and metabolic compromise, such as increasing glucose levels, reminiscent of premature aging [17592126]. | Fruit fly |
| mir-277 | — | Constitutive miR-277 expression shortens lifespan and synthetically lethal with reduced insulin signaling, indicating that metabolic control underlies this phenotype. Transgenic inhibition with a miRNA sponge construct also shortens lifespan [23669073].
miR-277 is downregulated during adult life [23669073].
mir-277 controls branched-chain amino acid catabolism and as a result it can modulate the activity of TOR kinase [23669073]. | Fruit fly |
| Sirt2 | — | Decreased expression of Sirt2 by RNA interference causes lethality during development. Silencing in neurons shortened mean lifespan by 20% [17159295]. | Fruit fly |
| Sirt6 | — | Decreased expression of Sirt6 by RNA interference causes lethality during development. Sirt6 silencing in neurons shortens mean lifespan by 20% [17159295]. | Fruit fly |
| Scgdelta | Sarcoglycan delta | Deletion of Scgdelta has detrimental effects on the flight muscles of adult animals and heart function. Median lifespan is reduced by 15-30% [17855453]. | Fruit fly |
| SNF4Agamma | SNF4/AMP-activated protein kinase gamma subunit | Deletion of SNF4Agamma from the first day of the imaginal stage shortens mean lifespan by 23% and causes morphological and behavioural features of premature aging [18219227]. | Fruit fly |
| DLP | Daxx-like protein | DLP mutants have a 20% shorter mean lifespan and reduced female fertility [17933869]. | Fruit fly |
| elav | embryonic lethal abnormal vision | elav mutation significantly decreases the lifespan. Median lifespan in males is 66% lower [20589912]. | Fruit fly |
| foxo | Forkhead box, sub-group O | foxo overexpression extends lifespan. Activation of foxo in the adult pericerbral fat body is sufficient for lifespan extension [15175753]. Overexpression of foxo in the adult adipose tissue alone prolongs lifespan [15192154; 15175753]. Limited activation of foxo reduces the expression of Drosophila insulin-like peptide dilp-2 synthesized in neurons and, represses endogenous insulin-dependent signaling in peripheral fat body [15175753]. foxo is not required for DR, but its activity modulates the response. foxo null mutants are highly and significantly shorter-lived than wild-type on all food dilutions apart from 0.1 SY and under starvation. foxo null mutants are not more sensitive to starvation than wild-type. foxo overexpression in adult fat body under normal nutritional conditions leads to extension of lifespan of females and causes a right shift of the response curve of lifespan to DR [18241326].
Overexpression of dFOXO in adult fat body increases median, by 21-33%, and maximum lifespan as well as lowers the age-specific mortality at all ages, in two independent experiments. Overexpression of dFOXO increases lifespan by lowering the whole mortality trajectory, with no effect on slope (similar to DR). Initiation of dFOXO expression at different ages increases subsequent lifespan with the magnitude of increase decreasing as the animals were put on RU486 (which activates the foxo transgene via UAS) at older ages. The effects of removal of dFOXO overexpression at different ages closely mirrored those of induction of expression and produce shortest lifespan observed in animals taken of RU486 at the earlier ages [17465980].
| Fruit fly |
| Gadd45 | growth arrest and DNA damage-inducible gene 45 | 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]. | Fruit fly |
| Hk | Hyperkinetic | Genetic mutation in Hyperkinetic shortens lifespan through acceleration of the aging process. At 25 degree Celsius mean and maximum lifespan is reduced by 29 and 32%, while by 18 degree Celsius the reduction is 59 and 39% [8582611]. | Fruit fly |
| Sh | Shaker | Genetic mutation in Sh decreases lifespan by accelerating the aging process. At 25 degree mean and maximum lifespan is reduced by 16 and 22%, while by 18 degree Celsius the reduction is 32 and 21% [8582611]. | Fruit fly |
| GstS1 | Glutathione S transferase S1 | GstS1 overexpression increases the mean lifespan by 33% [18059160]. | Fruit fly |
| Pi3K92E | Phosphatidylinositol-3-kinase | Heterozyogous mutation in Pi3K92E fails to extend lifespan [11292874] and it is recessive lethal.
Overexpression of a dominant-negative Pi3K92E (DP110) results in mutants that have impaired regeneration of the intestinal epithelium and are short lived with a reduction of the mean lifespan by 2.8% for males and 5.0% for females [20976250]. | Fruit fly |
| mle | maleless | Homozygous mutant animals (mle napts) display a shortened median lifespan and increased frailty in both males and females [18208580]. | Fruit fly |
| Pten | — | Increased Pten and 4E-BP activity in muscles is extends the lifespan [21111239]. | Fruit fly |
| Akh | Adipokinetic hormone | 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 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].
Fat-body specific Akh RNAi results in increased spontaneous activity and a small but significant increase in lifespan upon AL [22768842].
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]. | Fruit fly |
