| 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 | — | — | — |
| Ilp2 mutation | Ilp2 null mutants are significant longer-lived with a 8-13% longer median lifespan [20195512]. | Fly | — | +8 to +13 | — |
| 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 |
| 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 | — |
| 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 | — | — | — |
| Sir2 mutation | A decrease in Sir2 (alias dSir2) blocks the life-extending effect of caloric reduction or rpd3 mutations [15520384]. Sir2 mutation does not reduce lifespan under AL [15520384]. | 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 | — |
| Dominant-negative S6k | Ubiquitous overexpression of a dominant-negative form of S6k (alias dS6K) increases mean lifespan by 22%. Overexpression of a dominant-negative form of S6k protects mutants from deleterious effects of rich food, as if mimicking the effect of DR [15186745]. | Fly | +22 | — | — |
| Constitutive active S6k overexpression | Overexpression of a constitutively active form of S6k (alias dS6K) decreases mean lifespan by 34% at 29°C [15186745]. | Fly | -34 | — | — |
| 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 |
| 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 |
| Heterozygous hypomorphic Rpd3 mutation | Males heterozygous for hypomorphic (partial loss-of-function) mutation of Rpd3 have a lifespan extension of 33%. Females heterozygous for a hypomorphic allele have a 52% increase in lifespan. Longevity increases to the same extent in wild-type under low-calorie diet and rpd3 mutants fed normal diet [12459580]. | Fly | +33 to 52 | — | — |
| Heterzygous Rpd3 null mutation | Males heterozygous for a null mutation of Rpd3 have a lifespan extension of 41 - 47%. 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 [12459580]. | Fly | +41 to +47 | — | — |
| Bmcp knockout | 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]. | Fly | — | — | — |
| aPKC transposition | Insertion of a P-based vectors in the structural part of aPKC increase male and female lifespan [22661237]. | Fly | — | — | — |
| esg transposition | Disruption of esg by insertion of the P{GT1} vector 300 bp downstream of its structural part increases male and female lifespan [22661237]. | Fly | — | — | — |
| insc transposition | insc disruption through an insertion of the P{EPgy2} vector in ts structural part prolongs female lifespan [22661237]. | Fly | — | — | — |
| bchs mutation | 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]. | Fly | -28 to -54 | — | -24 to -46 |
| 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 | — | — | — |
| Pi3K92E mutation | Heterozyogous mutation in Pi3K92E fails to extend lifespan [11292874] and it is recessive lethal. | 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 | — | — |
| EcR mutation | 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]. | Fly | +40 to +50 | — | — |
| mth mutation | 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]. | Fly | +35 | — | +36 |
| 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 |
GenAge
GenDR
