| DLP mutation | DLP mutants have a 20% shorter mean lifespan and reduced female fertility [17933869]. | Fly | -20 | — | — |
| Prx5 mutation | dprx5(-/-) null mutants are comparatively more susceptible to oxidative stress, have higher incidence of apoptosis, and a shortened mean lifespan, but thee is no significant difference in maximum lifespan (10% survival) [21826223]. | Fly | — | — | — |
| dys RNAi | dys RNAi-mediated knockdown in the mesoderm shortens lifespan [18221418]. | Fly | — | — | — |
| elav mutation | elav mutation significantly decreases the lifespan. Median lifespan in males is 66% lower [20589912]. | Fly | — | — | — |
| Dominant negative Tor | Expression of a dominant-negative form of Tor extends lifespan [15186745]. Ubiquitious overexpression of dTOR with the da-GAL4 driver of UAS-dTOR(FRB) which contains the 11kDA FKB12-rapamycin binding domain led to a mean and maximum lifespan increase of 15% (24%) and 29% at 29°C and of 50% (26%) and 13% at 25°C, respectively [15186745].
Overexpression of the dominant-negative form of Tor specifically in the fat and muscle tissues is sufficient to extend the mean and maximum lifespan by 24 and 19%, respectively [15186745].
Overexpression of UAS-dTOR(WT) or UAS-dTOR(TED) prevents eclosion to adulthood [15186745]. | Fly | +15 to +50 | +13 to +29 | — |
| p53 dominant negative overexpression | Expression of dominant-negative versions of p53 in adult neurons extends lifespan by 58% in females and by 32% in males and increases resistance to genotoxic stress and resistance to oxidative stress, but not to starvation or heat stress, while not affecting egg production or physical activity. Dominant negative Dmp53 expression cancels out lifespan extension effect of DR, low calorie-food (5% SY). Muscle or fat body specific expression of a dominant negative form of Dmp53 as well as globally lack of Dmp53 decreases lifespan [16303568].
Expression of dominant-negative (DN) form of p53 in adult neurons, but not in muscle or fat body cells, extends median lifespan by 19% and maximum lifespan by 8%. The lifespan of dietary-restricted flies is not further extended by simultaneously expressing DN-DMp53 in the nervous system, indicating that a decrease in Dmp53 activity may be part of the DR lifespan-extending effect. Selective expression of DN-Dmp53 in only the 14 insulin-producing cell (IPCs) in the brain extends lifespan to the same extent as expression in all neurons and this lifespan extension is not additive with DR [17686972].
| Fly | +32 to +58 | +19 | +8 |
| 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 | — | — | — |
| mld heterozygous mutation | Female, but not male, heterozygous mutants display a 42% increase in mean lifespan at 29 degrees Celsius. DTS-3 +/- female adults exhibit a 50% reduced ecdysone titer and reduced fertility [12610309]. Female, but not male, heterozygoutes also exhibit a temperature-dependent increase in starvation resistance. | Fly | +42 | — | — |
| l(3)DTS3 mutation | Female, but not male, heterozygous mutants exhibit a 42% increase in mean lifespan [12610309]. | Fly | +42 | — | — |
| 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 |
| 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 | — |
| Wings ablation/clipping | Flies on DR who could not move or had inhibited fat metabolism in their muscle and do not get an extended lifespan. Flies with ablated wings caused by overexpressing reaper (UAS-rpr) with a wing-sepcific Gal4 enhancer trap (1096-Gal4) exhibit only a 14% extension in lifespan compared to controls which exhibit a 61% extension upon DR. Clipped wing flies exhibit a modest 33% increase, while controls exhibit a 97% lifespan extension upon DR Lifespan reduction upon DR by curtailing movement is specific to control animals as lifespan is not futher reduced with Akh inhibition [22768842].
Control and clipped-wing flies exhibit a similiar level of fat synthesis and breakdown. Muscle specific RNAi of Akh, CG7834, or CG4389 results in a significant reduction in movement of flies upon DR [22768842]. | 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 |
| foxo mutation | 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 [18241326]. | Fly | — | — | — |
| Hk mutation | 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]. | Fly | -29 to -59 | — | -32 to -39 |
| Sh mutation | Genetic mutation in Sh decrease lifespan by accelerating the aging proces. 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]. | Fly | -16 to -32 | — | -21 to -22 |
| p53 mutation | Globally lack of p53 decreases lifespan [16303568]. Loss of p53 activity slightly shortens the lifespan. Mutants that lack p53 survive well up to 50 days, but mortality rate increases relative to wild-type at later ages. p53 mutant animals are extremely sensitive to irradiation [12935877]. | Fly | — | — | — |
| Gr63a mutation | Gr63a loss-of-function in female flies leads to 30% extended mean lifespan, increased fat deposition, and enhanced resistance to some (but not all) environmental stresses. Lifespan of males is not extended [20422037]. | Fly | +30 | — | — |
| 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 | — | — | — |
| Pi3K92E mutation | Heterozyogous mutation in Pi3K92E fails to extend lifespan [11292874] and it is recessive lethal. | Fly | — | — | — |
| Ilp2 mutation | Ilp2 null mutants are significant longer-lived with a 8-13% longer median lifespan [20195512]. | Fly | — | +8 to +13 | — |
| Ilp2 RNAi | Ilp2 RNA interference results in a 24% to 47% increase in median lifespan [19005568]. | Fly | — | +24 to +47 | — |
| Ilp3 mutation | Ilp3 null mutants have a normal lifespan under AL and a normal DR response. Ilp2 Ilp3 Ilp5 triple null mutants fail to have a normal response to DR. Their response is right shifted, with mutants being shorter-lived compared to wild-type on low but longer-lived on high yeast concentrations [20195512]. | Fly | — | — | — |
| Ilp2/Ilp3/Ilp5 mutation | Ilp5 null mutants have a normal lifespan under AL and a normal DR response. Ilp2 Ilp3 Ilp5 triple null mutants fail to have a normal response to DR. Their response is right shifted, with mutants being shorter-lived compared to wild-type on low but longer-lived on high yeast concentrations [20195512]. | Fly | — | — | — |
| InrGC25/InrE19 transheterozygous mutation | InrGC25/InrE19 transheterozygous animals are short-lived an exhibit an elevated rate of age-independent mortality [11292874]. | Fly | — | — | — |
GenAge
GenDR
