| Tor | Target of rapamycin | 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]. | Fruit fly |
| Surf1 | surfeit gene 1 | 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]. | Fruit fly |
| sdhC | succinate dehydrogenase, cytochrome b556 subunit | Mutants expressing a dominant negative form of sdhC in the nervous system have a 22% reduced mean lifespan and signs of oxidative stress induction [17854771]. | Fruit fly |
| sun | Stunted | sun mutations increases lifespan and resistance to oxidative stress [15133470] | Fruit fly |
| snz | snazarus | 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]. | Fruit fly |
| S6k | RPS6-p70-protein kinase | Ubiquitous overexpression of a dominant-negative form of S6k (alias dS6K) increases mean lifespan by 22% and overexpression of a constitutively active form of S6k decreases mean lifespan by 34% at 29°C. Overexpression of a dominant-negative form of S6k protects mutants from deleterious effects of rich food, as if mimicking the effect of DR [15186745]. | Fruit fly |
| puc | puckered | 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]. | Fruit fly |
| pex13 | peroxin 13 | Mutation of pex13(KG04339), located in its promoter region, results in lower gene expression and increased lifespan by around 16% and 13% in males and females. pex13 mutation increases mean and maximum lifespan by 23-27/14-19% and 11%, respectively [22509016]. | Fruit fly |
| pex1 | peroxin 1 | Mutation of the promoter region of pex1(S4868), results in lower expression levels and increases lifespan in males and females by 16% and 13%, respectively. pex1 mutation increases mean and maximum lifespan and males/females by 27-23/14-19% and 0-15%, respectively [22509016]. | Fruit fly |
| Orco | Odorant receptor co-receptor | 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 Orco 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].
| Fruit fly |
| mld | molting defective | 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. | 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 |
| mth | methuselah | Mutants in mth display approximately 35% and 36% increase in average and maximum lifespan as well as enhanced resistance to various forms of stress (including starvation, high temperature, and dietary paraquat) [9794765].
Reduced expression of mth targeted only to the insulin-producing cells of the brain is sufficient to extend lifespan and to enhance oxdative stress resistance [23121290].
IPC-targeted overexpression of β-arrestin alone mimics the longevity phenotype of reduced mth signaling [23121290]. | Fruit fly |
| Loco | locomotion defects | Reduced expression of Loco due to hetero-deficient results in a 17-20% longer mean lifespan for both male and females, besides the fact that the homozygous deficiency of loco is lethal. Several of these long-lived mutants are more resistant to stresses such as starvation, oxidation and heat. Additionally, mutants have higher Manganese-containing superoxide dismutase (MnSOD) activity, increased fat content an diminished cAMP levels. Loco's RGS domain is required for the regulation of longevity as deletion analysis suggest [21776417]. | Fruit fly |
| l(3)DTS3 | lethal (3) DTS3 | Female, but not male, heterozygous mutants exhibit a 42% increase in mean lifespan and resistance to various stresses, with no apparent deficit in fertility or activity [12610309]. | Fruit fly |
| LBR | Lamin B receptor | Overexpression of Lamin B receptor in the adult muscle and in the abdominal fat body results in a 54% and 46% reduction of mean lifespan, respectively [18494863]. | Fruit fly |
| kuk | kugelkern | Overexpression of kugelkern in the adult muscle results in a 60% reduction of mean lifespan [18494863]. | 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| Rpd3 | Histone deacetylase Rpd3 | Males heterozygous for hypomorphic (partial loss-of-function) or null mutation of Rpd3 have a lifespan extension of 33% and 41 - 47%, respectively. Females heterozygous for a hypomorphic allele have a 52% increase in lifespan, but females carrying a null mutation have only modest increase in maximum lifespan (but not median lifespan). Longevity increases to the same extent in wild-type under low-calorie diet and rpd3 mutants fed normal diet. DR fails to further increase lifespan of rpd3 mutants. DR leads to a moderate but significant down-regulation of Rpd3, analogous to decrease obtained in heterozygotes carrying rpd3 mutation. rpd3 mutants fed normal food and wild-type fed low-calorie increase Sir2 expression two-fold [12459580]. | 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 |
| 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 |
