| 14-3-3epsilon | CG31196 gene product from transcript CG31196-RA | 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]. | Fruit fly |
| alpha-Man-I | alpha Mannosidase I | 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%. alpha-Man-I RNAi knockdown results in a 39% increase in mean lifespan [19302370]. | Fruit fly |
| aPKC | atypical protein kinase C | Insertion of a P-based vectors in the structural part of aPKC increase male and female lifespan [22661237]. | Fruit fly |
| bchs | blue cheese | Loss of function mutation in bchs results in a 40-45% decrease in mean lifespan and is associated with age-related neurodegenerative phenotype with reduced CNS size and altered morphology as well as accumulation of insoluble ubiquinated proteins and amyloid precursor-like proteins along with an increase in neuronal apoptosis. No pronounced developmental defects were observed and young adults have normal behaviours, indicating that the bchs gene is essential for normal adult survival and longevity [12598614].
bchs mutation reduces mean lifespan by 28 - 54% and maximum lifespan by 24 - 46% [17435236].
Alfy (autophagy-linked FYVE protein) is the conserved human bchs homolog [15292400]. | Fruit fly |
| Bmcp | Mitochondrial uncoupler | Bmcp knockout flies live longer on low-calorie diets, have a decreased fertility, and gain less weight on high-calorie diets. Bmcp (ucp5) knockout mutants live longer than wild-type on low-calorie diets, but no longer on starvation or high-calorie diets. Ectopic neuronal expression of Bmcp transgene rescues starvation sensitive phenotype of Bmcp knockout mutants [16387864]. | Fruit fly |
| bwa | brain washing | bwa (alias Dacer) inactivation increases Drosophila pre-adult development time and anti-oxidative stress capacity. Mean lifespan is increased by 16% in females, by 21% in males and by 19% in total. Maximum lifespan of females, males is also extended by 20 and 12%, respectively [20112046]. | Fruit fly |
| CG17856 | — | RNAi of CG17856 results in an increase in mean lifespan of 13-18% in females. In the case of males and post-developmental experiments the results are variable [19747824]. | Fruit fly |
| CG18809 | — | RNAi of CG18809 results in a 7-19% increase in mean lifespan of females, while neural RNAi results in an increased mean lifespan of up to 12% in females. For males the results are variable [19747824]. | 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 |
| CG5389 | — | RNAi of complex V subunit CG5389 results in increased mean longevity under standard laboratory food conditions (3% yeast) in males. RNAi started from the development results in a mild lifespan increase in both sexes (3-11% in females and 3-8% in males). Post-developmental RNAi and silencing limited to neurons has variable effects with reduction in lifespan of up to 9% [19747824]. Under rich media conditions CG5389 knockdown throughout development and adulthood increases mean lifespan by 26% and abolished the lifespan extension by DR (started in the adulthood) in males. Suppression of CG5389 only during the adulthood either via RNAi by tub-GS or via oligomycin (a specific inhibitor of complex V) feeding prevents an increase in longevity under DR (started in the adulthood) in males [19968629]. | Fruit fly |
| CG9172 | — | RNAi against CG9172 increases mean lifespan in females by up to 4-12% when applied in both development and adulthood, and up to 46% when applied in adult neurons only. For males the effect is variable [19747824]. | Fruit fly |
| chico | Insulin receptor substrate-1 | Mutation in chico extends mean, median, and maximum lifespan by 56%, 48%, and 42% in homozygotes and 44%, 36%, and 35% in heterozygotes. chico mutation produces dwarf, long-lived females at normal nutrition. Male heterozygous live 13% longer than wild-type, but male homozygous have a shortened lifespan [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]. chico heterzoygous females have a reduced fecundity and homozygous recessive mutants are sterile. chico heterozygous mutants are resistant to starvation but not oxidative stress or temperature stress [11292874]. | Fruit fly |
| DNApol-gamma35 | DNA polymerase gamma 35kD | Overexpression of DNApol-gamma35 (DNA polymerase gamma) in the nervous system results in a decrease in the median lifespan ranging from 39% to 52% [17999718].
| Fruit fly |
| dnc | dunce | cAMP phosphodiesterase-deficient dunce mutants have an extended maximum lifespan by about 70% [17369827]. | Fruit fly |
| E(z) | Enhancer of zeste | 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]. | Fruit fly |
| EcR | Ecdysone receptor | Mutant heterozygotes in EcR live on mean 40%-50% longer than controls [12610309; reviewed in 12610294]. Homozygous mutants in EcR are inviable. The developmental time and weight of EcR+/- mutants is the same as control, but resistance to temperature, oxidative stress, and starvation is increased in heterozygotes [12610309]. | Fruit fly |
| Edem1 | — | The mean lifespan of Edem1 mutants of both male and female is increased by more than 30% [19302370]. | Fruit fly |
| egm | enigma | Mutation in egm confers resistance to oxidative stress and extends the lifespan [16434470]. | Fruit fly |
| esc | extra sexcombs | Males heterozygous for the null esc4 or the dominant negative esc9 mutation that are progeny of an out-cross to a O-R wild-type strain have median lifespan that is, respectively, 47% and 60% longer than the O-R control. When derived from an out-cross to a longer-lived C-S wild-type strain, heterozygous esc9 flies have a median lifespan that is 43% longer than the C-S control [20018689]. | Fruit fly |
| esg | Escargot | Disruption of esg by insertion of the P{GT1} vector 300 bp downstream of its structural part increases male and female lifespan. Heterozygous esg and insc double mutants interact in the course of lifespan determination. The decrease of esg transcription is associated with lifespan increase in mutant esg and insc flies [22661237]. | Fruit fly |
| Gr63a | Gustatory receptor 63a | 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].
Overexpression of Gr63a has modest negative effect on lifespan [20422037]. | Fruit fly |
| Ilp2 | Insulin-like peptide 2 | 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].
Ilp2 RNA interference results in a 24% to 47% increase in median lifespan [19005568].
Ilp2 is transcriptional down-regulated in long-lived mutants. Ilp2 null mutants are significant longer-lived with a 8-13% longer median lifespan, but have 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 shorter-lived compared to wild-type on low but longer-lived on high yeast concentrations [20195512]. | Fruit fly |
| Indy | I'm not dead yet | 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]. | Fruit fly |
| InR | Insulin-like 1 receptor | Mutations in InR (InRE19/InRp5545 transheterozygous) result in dwarf females with extended lifespan of up to 85% and dwarf males with reduced late age-specific mortality (although no significant change in lifespan) [11292875]. InrGC25/InrE19 transheterozygous animals are short-lived an exhibit an elevated rate of age-independent mortality [11292874].
Natural allelic variation in InR are associated with variation in lifespan [15013662; 20074316]. | Fruit fly |
| insc | inscuteable | insc disruption through an insertion of the P{EPgy2} vector in ts structural part prolongs female lifespan. Heterozygous esg and insc double mutants interact in the course of lifespan determination. The decrease of esg transcription is associated with lifespan increase in mutant esg and insc flies [22661237]. | Fruit fly |
