| 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 | — | — |
| Neural-specific POSH overexpression | Neural-specific overexpression of POSH extends the mean lifespan of adult flies by 14% at 25°C. Ectopic expression of POSH during development results in morphological abnormalities [11868902]. | Fly | +14 | — | — |
| Sir2 overexpression | Overexpression of Sir2 (alias dSir2) extends lifespan by up to 57% and specifically median lifespan by 40-60%. Ubiquitous Sir2 overexpression causes a 4-fold increase in Sir2 mRNA expression and an up to 57% increase in average lifespan (29% for females and 18% for males). A 10 - 20% increase in Sir2 mRNA levels causes no lifespan extension. Neuronal Sir2 overexpression extends average lifespan by 52% in females and 20% in males. Motor-neuronal specific expression fails to cause lifespan extension. DR fails to cause further increase in lifespan or even reduces lifespan toward normal of dSir2 overexpression mutants [15520384]. Mild Sir2 overexpression in the fat-body extends lifespan and reduces relative body fat content in both males and females [22661237].
A diet-dependent lifespan phenotype of dSir2 overexpression in the fat-body, but not in muscles, negates the effects of background genetic mutants [23246004]. | Fly | +18 to + 57 | +4- to +60 | — |
| foxo overexpression | foxo overexpression extends lifespan. Activation of foxo in the adult pericerbral fat body is sufficient for lifespan extension [15175753]. Overexpression of foxo in the adult adipose tissue alone prolongs lifespan [15192154; 15175753]. Limited activation of foxo reduces the expression of Drosophila insulin-like peptide dilp-2 synthesized in neurons and, represses endogenous insulin-dependent signaling in peripheral fat body [15175753]. foxo overexpression in adult fat body under normal nutritional conditions leads to extension of lifespan of females and causes a right shift of the response curve of lifespan to DR [18241326].
Overexpression of dFOXO in adult fat body increases median, by 21-33%, and maximum lifespan as well as lowers the age-specific mortality at all ages, in two independent experiments. Overexpression of dFOXO increases lifespan by lowering the whole mortality trajectory, with no effect on slope (similar to DR). Initiation of dFOXO expression at different ages increases subsequent lifespan with the magnitude of increase decreasing as the animals were put on RU486 (which activates the foxo transgene via UAS) at older ages. The effects of removal of dFOXO overexpression at different ages closely mirrored those of induction of expression and produce shortest lifespan observed in animals taken of RU486 at the earlier ages [17465980]. | Fly | — | +21 to +33 | — |
| Gclm overexpression | Overexpression of Gclm extends the mean lifespan by up to 24% [16148000]. | Fly | +24 | — | — |
| mir-34 upregulation | mir-34 upregulation extends median lifespan and mitigated neurodegeneration induced by polyglutamine. | Fly | — | — | — |
| Sod overexpression | Simultaneous overexpression of catalase and Sod (alias Sod1) results in a one-third lifespan extension, a slower rate of mortality acceleration, and a delayed loss in physical performance, but neither has any effect on lifespan alone [8108730]. General overexpression of Sod (also known as Cu/ZnSOD) alone is sufficient to extend lifespan by up to 48%. Simultaneous overexpression of catalase with Cu/ZnSOD has no added benefit, presumably due to a pre-existing excess of catalase [9858546]. | Fly | +38 | — | — |
| TrxT overexpression | Overexpression of TrxT in neurons increases the level of locomotor activity in aged flies and extends the mean lifespan by 15% [17301052]. | Fly | +15 | — | — |
| UCP2 overexpression | Overexpression of human UCP2 in the fly nervous system extends lifespan by 10-30%. Ubiquitous overexpression is lethal [16054055]. | Fly | +10 to +30 | — | — |
| Atg2 overexpression | Atg2 overexpression increases average female lifespan by 28% [18059160]. | Fly | +28 | — | — |
| DNApol-gamma35 overexpression | 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]. | Fly | -39 to -52 | — | — |
| fh overexpression | Overexpression of fh in the mitochondria of female transgenic animals increases antioxidant capability, resistance to oxidative stress insults, and longevity [18258192]. | Fly | — | — | — |
| Gadd45 overexpression | Gadd45 overexpression in the nervous system leads to a significant increase of lifespan without a decrease in fecundity and locomotor activity. The lifespan extension effect is more pronounced in males than in females. Additional maximum lifespan is also extended. The maximum lifespan is increased by 50% and 59% for females and males, respectively. The median lifespan is extended by 46 and 77% for females and males, respectively [22661237]. | Fly | — | — | — |
| Gr63a overexpression | Overexpression of Gr63a has modest negative effect on lifespan [20422037]. | Fly | — | — | — |
| GstS1 overexpression | GstS1 overexpression increases the mean lifespan by 33% [18059160]. | Fly | +33 | — | — |
| hebe overexpression | Adult-specific overexpression of hebe increases the lifespan by 5-30% and modulates late-age female fecundity. Female and male mean lifespan is up to 11% and 24% higher [19011900]. | Fly | +5 to +30 | — | — |
| Hsc70-3 overexpression | Overexpression of Hsc70-3 increases average female lifespan by 27% [18059160]. | Fly | +27 | — | — |
| Hsp22 overexpression | Overexpression of mitochondrial Hsp22 in all cells or specifically in motorneurons (using GAL4/UAS binary system) increases life lifespan by 32% and resistance to oxidative stress [19948727; 20036725].
Ubiquitous or a targeted expression of Hsp22 within motorneurons increases the mean lifespan by more than 30%. Hsp22 shows beneficial effects on early-aging events since the premortality phase displays the same increase as the mean lifespan [14734639].
| Fly | +30 to 32 | — | — |
| Hsp22-promoter driven reporter overexpression | Hsp22-promoter driven reporter overexpression reduces mean and maximum lifespan [19420297]. | Fly | — | — | — |
| Jafrac1 overexpression | Neuronal overexpression of Jafrac1 significantly increases both mean and maximum lifespan, while neuronal knockdown as well as loss of function mutation, causes a reduction in lifespan by 30%. The mean lifespan is 26% and 29% higher in females and males, respectively. The maximum lifespan is increased by 22% and 26% in females and males, respectively [19720829].
There is a consistent and significant lifespan extension (15% mean lifespan increase) in both males and females when Jafrac1 is overexpressed in somatic cells. Jafrac1 overexpression using the weaker 5961FS driver moderately but significantly extends lifespan [20976250]. | Fly | +15 to +29 | +22 to +26 | — |
| CG3776 overexpression | Overexpression of CG3776 (alias Jhebp29) reduces the mean lifespan, where the reduction in males is slightly higher.
The lifespan of female and male flies with overexpressed CG3776 is reduced by 35% and 42.6%, respectively when compared with Oregon R flies [18275960].
| Fly | -35 to -42.6 | — | — |
| kuk Overexpression | Overexpression of kugelkern in the adult muscle results in a 60% reduction of mean lifespan [18494863]. | Fly | -60 | — | — |
| LBR overexpression | 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]. | Fly | — | — | — |
| magu overexpression | Adult-specific overexpression of magu increases lifespan by 5-30% and modulates late-age fecundity [19011900]. | Fly | +5 to +30 | — | — |
| Pten overexpression | Increased Pten and 4E-BP activity in muscles is extends the lifespan [21111239]. | Fly | — | — | — |
GenAge
GenDR
