| 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 |
| Atg2 | Autophagy-specific gene 2 | Atg2 overexpression increases average female lifespan by 28% [18059160]. | Fruit fly |
| Akt1 | CG4006 gene product from transcript CG4006-RA | 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]. | Fruit fly |
| Jafrac1 | thioredoxin peroxidase 1 | Neuronal overexpression of Jafrac1 significantly increases both mean and maximum lifespan, while neuronal knockdown as well as loss of function mutation, causes a reduction in lifespan by 30%. The mean lifespan is 26% and 29% higher in females and males, respectively. The maximum lifespan is increased by 22% and 26% in females and males, respectively [19720829].
There is a consistent and significant lifespan extension (15% mean lifespan increase) in both males and females when Jafrac1 is overexpressed in somatic cells. Jafrac1 overexpression using the weaker 5961FS driver moderately but significantly extends lifespan [20976250]. | Fruit fly |
| mir-14 | mir-14 stem loop | Mutating mir-14 decreases lifespan in both sexes. mir-14 reduces the mean and maximum lifespan of females by 55 and 36%, respectively, while those of males is reduced by 29 and 21%, respectively [12725740].
| Fruit fly |
| Dcr-2 | Dicer-2 | Median lifespan of homozyogous and transheterozyogous Dcr-2 mutants is reduced by 18-36% in males and by 27-36% in females. Dcr-2 loss changes the expression of mostly metabolic genes implicated in stress resistance and aging. Dcr-2 mutants are hypersensitive to oxidative, endoplasmic reticulum, starvation and cold stress as well as abnormal lipid and carbohydrate metabolism [21889502]. | Fruit fly |
| CG13890 | — | Overexpression of CG13890 (DCI) throughout the whole body increases mean and median lifespan by 35 and 31%, but decreases maximum lifespan by 6%, increases stress resistant (to paraquat and starvation), consistently reduces the mortality rate across adult ages and reduces the lifespan extension of DR by 15% [22997544].
CG6783 overexpression increases the dFOXO nuclear localization in the fat-body. mRNA levels of dFOXO target genes l(2)efl and 4E-BP in the adult whole bodies increases in response to overexpression of CG6783 [22997544]. | Fruit fly |
| fabp | fatty acid bindin protein | Overexpression of fabp (CG6783) throughout the whole body increases mean, median and maximum lifespan by 77, 81 and 13%, increases stress resistant (to paraquat but not starvation), consistently reduces mortality rate across adult ages and reduces the lifespan extension of DR by 12% [22997544].
fabp overexpression increases the dFOXO nuclear localization in the fat-body. mRNA levels of dFOXO target genes l(2)efl and 4E-BP in the adult whole bodies increases in response to overexpression of fabp [22997544].
Females of the genotype Act-GS-Gal4 > UAS-CG6783 exhibit an increase in median lifespan compared to uninduced control in response to feeding with RU486-containing food from day 3 of adulthood (P < 0.0001). Mean lifespan is extended by 10, while maximum lifespan is decreased by 11% [22997544]. | Fruit fly |
| Hsp22 | Heat shock protein 22 | Overexpression of mitochondrial Hsp22 in all cells or specifically in motorneurons (using GAL4/UAS binary system) increases life lifespan by 32% and resistance to oxidative stress [19948727; 20036725].
Ubiquitous or a targeted expression of Hsp22 within motorneurons increases the mean lifespan by more than 30%. Hsp22 shows beneficial effects on early-aging events since the premortality phase displays the same increase as the mean lifespan [14734639].
Animals that do not express Hsp22 (due to a transposition into its transcriptional starting site) have a 40% decrease in lifespan, exhibit a 30% decrease in locomotor activity and are sensitive to mild stress [20036725].
Doxycyline-regulated overexpression of Hsp22 makes animals more sensitive to heat and oxidative stress as well as reduces the mean lifespan by up to 21%, particularly at higher culture temperature [15491684].
Hsp22-promoter driven reporter overexpression reduces mean and maximum lifespan [19420297].
Histone deacetylase inhibitor Trichostatin A (TSA) extends the lifespan of *Drosophila melanogaster* by promoting the hsp22 gene transcription, and affecting the chromatin morphology at the locus of hsp22 gene along the polytene chromosome [15346199].
| Fruit fly |
| Hsp70Bb | Hsp70Bb Heat-shock-protein-70Bb | Overexpression of the Hsp70 locus (containing Hsp70Bb and Hsp70Bc) in transgenic flies extends lifespan as much as 7.9% [9363888]. | 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 |
| Eip71CD | Ecdysone-induced protein 28/29kD | Overexpression of Eip71CD (alias MsrA) in nervous system extends the lifespan by up to 70%, increased resistance to oxidative stress, and delays the onset of senescence-induced decline in activity levels and reproductive capacity. Eip71CD is a downstream effector of foxo [22310715].
Mean and maximum lifespan is increased by up to 2-% in animals that overexpress Eip71CD [20655917]. | Fruit fly |
| hep | hemipterous | Overexpression of hey significantly extends median (50%) and maximum (25%) lifespan. A hypomorphic allele of hep (hep1) laerlgy prevents lifespan extension caused by puc heterozygosity [14602080]. | 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 |
| 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 |
| 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 |
| 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 |
| Pink1 | PTEN-induced putative kinase 1 | Overexpression of Pink1 and overexpression of Pink1 with alpha-synclein results in an increase in lifespan which is accompanied by an increase in healthspan (as measured by mobility) when driven by a dopaminergic cells targeting TH-Gla4 transgene [22653599]. | Fruit fly |
| Thor | — | Null mutation in Thor (alias d4E-BP) causes a significant decrease in longevity (-25% median lifespan in males). Thor is strongly upregulated during starvation. foxo and Thor null mutants are compromised in stress resistant. Stress resistance of foxo null mutants is rescued by Thor overexpression [16055649]. Thor is upregulated on the protein level in a foxo-independent manner upon DR, while it is transcriptional induced in a foxo-dependent fashion by starvation. Thor null mutants cancel out DR-induced lifespan extension, because mutants exhibit a diminished change in lifespan when nutrient conditions were varied. Ubiquitously expression of Thor rescued DR response in females and males. Thor null mutants have a wild-type similar reduction in egg production upon DR. Ubiquitously overexpression of wild-type Thor causes no change under AL, but an activated allele (with more than 3-fold increased binding activity to delF4E) significantly extends lifespan of females (weak allele) and females as well as males (strong allele). Mean lifespan is extended by 11 to 40%. Median lifespan of males and females is enhanced by by 11 and 22%, respectively. Maximum lifespan is extended by 16 and 18% for males and females, respectively. Under DR (0.25% YE) there is no lifespan extension, beyond the effect of DR alone, in all (wild-type, weak and strong) Thor alleles [19804760].
Lifespan of animals with increased Pten and 4E-BP activity in muscle exhibit and extended mean and maximum lifespan by 20% and 15.8% [21111239]. | Fruit fly |
| CG10916 | Mediator complex subunit 9 | Overexpression of CG10916 in males increases mean and maximum lifespan by 27% and 26%, respectively [22366109]. | Fruit fly |
| PGRP-LF | Peptidoglycan recognition protein LF | Overexpression of PGRP-LF increases mean and maximum lifespan by 13% and 24% [22366109]. | Fruit fly |
| CG30427 | — | Overexpression of CG30427 in males increases mean lifespan by 18% [22366109]. | Fruit fly |
| CG10383 | — | Overexpression of CG10383 in males increases mean and maximum lifespan by 12% and 8%, respectively [22366109]. | Fruit fly |
| SIFR | SIFamide receptor | Overexpression of SIFR in males extends mean and maximum lifespan by 23% and 3%, respectively [22366109]. | Fruit fly |
| sm | smooth | Overexpression of sm in males increases mean and maximum lifespan by 29% and and 16%, respectively [22366109]. | Fruit fly |
