| Rbp9 mutation | Rbp9 mutation significantly decreases longevity with a 33% reduction in median lifespan of males [20589912]. | Fly | — | -33 | — |
| Thor mutation | Null mutation in Thor (alias d4E-BP) causes a significant decrease in longevity (-25% median lifespan in males). foxo (alias dFOXO) and Thor null mutants are compromised in stress resistant. Stress resistance of foxo null mutants is rescued by Thor overexpression [16055649]. Thor null mutants cancel out DR-induced lifespan extension, because mutants exhibit a diminished change in lifespan when nutrient conditions were varied. Thor null mutants have a wild-type similar reduction in egg production upon DR [19804760]. | Fly | — | -25 | — |
| Nlaz mutation | 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]. | Fly | — | -22.5 to -30.8 | -12 to -30 |
| Scgdelta deletion | Deletion of Scgdelta has detrimental effects on the flight muscles of adult animals and heart function. Median lifespan is reduced 15-30% [17855453]. | Fly | — | -15 to -30 | — |
| Lnk mutation | Loss of Lnk function results in increased median (14% in females and 17.5 in males) and maximum lifespan, reduced female fecundity and improves survival under conditions of oxidative stress and starvation. Heterozygousity does not result in any significant differences in lifespan in either males or females. Moreover, lifespan extension in one of the female homozygous mutant is fully rescued by the introduction of a Lnk genomic rescue construct [20333234]. | Fly | — | -14 to -17.5 | — |
| Sir2 RNAi | Decreased expression of Sir2 and Sir2-like genes in all cells causes lethality during development. Suppression of the Sir2 in neurons decreases the median lifespan by 10-30%, while ubiquitous silencing of the Sir2-like genes shortens lifespan. The effects are server at 28°C that at 25°C [17159295]. | Fly | — | -10 to -30 | — |
| Ilp2 mutation | Ilp2 null mutants are significant longer-lived with a 8-13% longer median lifespan [20195512]. | Fly | — | +8 to +13 | — |
| snz mutation | Mutation in snz increases maximum lifespan of both sexes by up to 66%, while the median female lifespan is approximately 85% higher and that of males around 72% [18478054]. | Fly | — | +72 to +85 | +66 |
| Orco mutation | Loss-of-function mutation in Orco (alias Or83b) results in olfactory defects, altered adult metabolism, enhanced stress resistance, and life-extension. Fully fed female homozygous Or83b null mutants exhibit a 56% increase in median lifespan and a 30% increase in maximum lifespan. Males are also significantly longer-lived, though to a smaller degree and maximum lifespan is not extended. Heterozygous mutants of both sexes show an intermediate longevity. Lifespan of homozygous Or83b null mutants is further increased by DR, but the relative increase in median and mean longevity is significantly greater when mutants were maintained in well-fed conditions [17272684]. | Fly | — | +56 | +30 |
| Homozygous chico mutation | Mutation in chico extends mean, median, and maximum lifespan by 56%, 48%, and 42% in homozygotes. chico mutation produces dwarf, long-lived females at normal nutrition [11292874]. Wild-type and chico mutant females have similar peak lifespan under DR, but the food concentration at which these are achieved is shifted to higher amounts. chico mutation induces a state equivalent to submaximal, DR-induced slowing of aging [11951037]. Male chico homozygous have a shortened lifespan [11292874]. Female chico homozygous recessive mutants are sterile [11292874]. | Fly | +56 | +48 | +42 |
| Heterzygous chico mutation | Mutation in chico extends mean, median and maximum lifespan by 44%, 36% and 35% in heterozygotes. chico mutation produces dwarf, long-lived females at normal nutrition [11292874]. Wild-type and chico mutant females have similar peak lifespan under DR, but the food concentration at which these are achieved is shifted to higher amounts. chico mutation induces a state equivalent to submaximal, DR-induced slowing of aging [11951037]. Male chico heterozygous live 13% longer than wild-type [11292874]. chico heterzoygous females have a reduced fecundity. chico heterozygous mutants are resistant to starvation but not oxidative stress or temperature stress [11292874]. | Fly | +44 | +36 | +35 |
| 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 | — |
| Ilp2 RNAi | Ilp2 RNA interference results in a 24% to 47% increase in median lifespan [19005568]. | Fly | — | +24 to +47 | — |
| Igf1 overexpression | Cardiac specific overexpression of Igf1 results in a 23% increase in median lifespan, though no increase in maximum lifespan [17973971]. | Fly | — | +23 | — |
| 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 |
| 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 | — |
| 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 |
| 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 | — | — | — |
| Sod mutation | Sod mutant flies display infertility and a reduction in lifespan [2539600]. | Fly | — | — | — |
| sun mutation | sun mutations increases lifespan and resistance to oxidative stress [15133470] | 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 | — | — | — |
| 14-3-3epsilon mutation | Loss of 14-3-3ε results in increased stress-induced apoptosis, growth repression and extended lifespan of flies, in a foxo-dependent manner. Mean lifespan of males and females is increased by 25% and 49%, respectively. Increased 14-3-3ε expression also reverts foxo-induced growth defects. No effect of lifespan is observed when overexpressing 14-3-3ε in adipose tissue, indicating that endogenous foxo activity in this tissue is low under normal conditions [18665908]. | Fly | +25 to +49 | — | — |
| 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 | — | — | — |
GenAge
GenDR
