| fabp overexpression | Overexpression of fabp (CG6783) throughout the whole body increases mean, median and maximum lifespan by 77, 81 and 13%, increases stress resistant (to paraquat but not starvation), consistently reduces mortality rate across adult ages and reduces the lifespan extension of DR by 12% [22997544].
fabp overexpression increases the dFOXO nuclear localization in the fat-body. mRNA levels of dFOXO target genes l(2)efl and 4E-BP in the adult whole bodies increases in response to overexpression of fabp [22997544].
Females of the genotype Act-GS-Gal4 > UAS-CG6783 exhibit an increase in median lifespan compared to uninduced control in response to feeding with RU486-containing food from day 3 of adulthood (P < 0.0001). Mean lifespan is extended by 10, while maximum lifespan is decreased by 11% [22997544]. | Fly | +77 | +81 | +13 |
| MSRA overexpression | Animals engineered to overexpress bovine MSRA in the nervous system have an extended median lifespan by up to 70% (relative to parental control), increased resistance to oxidative stress, and delayed the onset of senescence-induced decline in activity levels and reproductive capacity [11867705]. | Fly | — | +70 | — |
| hep overexpression | Overexpression of hey significantly extends median (50%) and maximum (25%) lifespan [14602080]. | Fly | — | +50 | +25 |
| 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 | — |
| Akh overexpression | Overexpression of Akh in a ubiquitousness manner enhances fat metabolism (significant increase in triglyceride synthesis and breakdown under AL), spontaneous activity (148% on AL and 154% on DR), and lifespan on AL (33%). However, despite and increase in movement under DR, lifespan is not increased under a restricted diet [22768842]. | Fly | — | +33 | — |
| Spargel overexpression | Tissue-specific overexpression of dPGC-1 in stem and progenitor cells within the digestive tract of females flies extends the median and maximum lifespan of females by up to 33% and 37%. Those mutants display a delay in the onset of aging-related changes in the intestine, leading to improved tissue homoeostasis in old flies [22055505]. | Fly | — | +33 | +37 |
| CG13890 overexpression | Overexpression of CG13890 (DCI) throughout the whole body increases mean and median lifespan by 35 and 31%, but decreases maximum lifespan by 6%, increases stress resistant (to paraquat and starvation), consistently reduces the mortality rate across adult ages and reduces the lifespan extension of DR by 15% [22997544].
CG6783 overexpression increases the dFOXO nuclear localization in the fat-body. mRNA levels of dFOXO target genes l(2)efl and 4E-BP in the adult whole bodies increases in response to overexpression of CG6783 [22997544]. | Fly | +35 | +31 | +6 |
| Lazarillo supplementation | Extracellular forms of Laz have autocrine and paracrine protecting effects for oxidative stress-challanged Drosophila S2 cells. Local effects of GPI-linked Laz inside and outside the nervous system promote survival upon different stress forms, and extend lifespan and healthspan of the flies in a cell-type dependent manner. Ectopic enhancement of Laz expression increases mean, median, and maximum lifespan. Laz overexpression (via the use of a ubiquitous da-GAL4 driver) increases median lifepan by 28.3% (p < 0.0005). Overexpression of Laz specifically in muscles and brain (via GAL4109(2)80 driver) increases median lifespan by 43.5%. Laz overxpression in dopaminergic and serotenergic neurons and epidermis increases median lifespan bt 31.4% (p < 0.0005) [22846641]. | Fly | — | +28.3 to +43.5 | — |
| 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 | — |
| 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 | — |
| Hsp68 overexpression | Overexpression of Hsp68 extends modestly (by around 15%) median and maximum lifespan [14602080].
There is a consistent and significant lifespan extension by 20% in both males and females when hsp68 is overexpressed in somatic cells. hp68 overexpression using GMR-Gal4, and eye-specific driver that expresses Gal4 in salivary glands has no effects.Hsp78 overexpression using the weaker 5961FS driver moderately but significantly extends lifespan [20976250]. | Fly | +20 | +15 | +15 |
| Thor overexpression | Ubiquitously overexpression of wild-type Thor (alias d4E-BP) causes no change under AL, but an activated allele (with more than 3-fold increased binding activity to delF4E) significantly extends lifespan of females (weak allele) and females as well as males (strong allele). Mean lifespan is extended by 11 to 40%. Median lifespan of males and females is enhanced by by 11 and 22%, respectively. Maximum lifespan is extended by 16 and 18% for males and females, respectively. Under DR (0.25% YE) there is no lifespan extension, beyond the effect of DR alone, in all (wild-type, weak and strong) Thor alleles [19804760].
Lifespan of animals with increased Pten and 4E-BP activity in muscle exhibit and extended mean and maximum lifespan by 20% and 15.8% [21111239]. | Fly | +11 to +40 | +11 to +22 | +16 to +18 |
| Pink1 overexpression | Overexpression of Pink1 and overexpression of Pink1 with alpha-synclein results in an increase in lifespan which is accompanied by an increase in healthspan (as measured by mobility) when driven by a dopaminergic cells targeting TH-Gla4 transgene [22653599]. | Fly | — | — | — |
| Ef1alpha48D overexpression | Overexpression of Ef1alpha48D (transformed with a P-element vector and under control of hsp70 regulatory sequences) results in lifespan extension by 18-41% [2508089]. | Fly | +18 to +41 | — | — |
| Mt2 overexpression | Overexpression of Mt2 extends mean and maximum lifespan [15533947]. | Fly | — | — | — |
| GLaz overexpression | Overexpression of GLaz results in increased resistance to hyperoxia (100% O2) and a 29% extension of mean lifespan under normoxia. Lifespan was also extended 30-60% under starvation [16581512]. | Fly | +29 | — | — |
| Hsp26 overexpression | Overexpression of Hsp26 (by the UAS/GAL4 system) increases stress resistance and extends the mean lifespan by 30% [15308776]. | Fly | +30 | — | — |
| Hsp27 overexpression | Overexpression of Hsp27 (by the UAS/GAL4 system) increases stress resistance and extends the mean lifespan by 30% [15308776]. | Fly | +30 | — | — |
| MAPT overexpression | Expression of wild-type human MAPT (tau) moderately shortened lifespan. Expression of a mutant form of human MAPT (Arg406 Trp), associated with an early onset familial form of demetia, results in a several shortened lifespan. MAPT is implicated in the pathogenesis of Alzeimer's disease and related disorders in humans. Transgenic flies exhibit key features of the human disorders: adult onset, progressive neurodegeneration, early death, enhanced toxicity of mutant tau, accumulation of abnormal tau, and relative anatomic selectivity. However, neurodegeneration occurred without the neurofibrillary formation that is observed in humans disease and some rodent taupathy models [11408621]. | Fly | — | — | — |
| Rdh overexpression | Overexpression of Rdh from a doxycycline-inducible promoter results in a 6-17% increase in mean lifespan [12620118].
Rdh is an open reading frame in the first intron of the encore gene [12620118]. | Fly | +6 to +17 | — | — |
| sug overexpression | Overexpression of sug (from a doxycycline-inducible promoter) results in a 5-9% increase in mean lifespan [12620118]. | Fly | +5 to +9 | — | — |
| VhaSFD overexpression | Overexpression of VhaSFD (from a doxycycline-inducible promoter) results in a 5-10% increase in mean lifespan [12620118]. | Fly | +5 to +10 | — | — |
| Trxr-1 overexpression | Overexpression of Trxr-1 (alias GSR; glutathione reductase) in transgenic flies results in increased lifespan and oxidative stress resistance, but only under hyperoxia [10506576]. | Fly | — | — | — |
| Cbs overexpression | Ubiquitous or neuron-specific transgenic overexpression of Cbs enhances longevity in fully-fed animals.
Adult-specific ubiquitous expression of Cbs is sufficient to increase female mean and maximum lifespan by 12 - 43% and 10%, respectively. Males, whose lifespan is relatively less affected by DR, exhibite a smaller, but still significant increase in lifespan by 7% upon Cbs overexpression. Neuronal overexpression also increases lifespan, albeit modestly (approximately 12% mean and 15% maximum lifespan extension), whereas overexpression in the fat body and in the gut has no effect [21930912]. | Fly | +12 to +43 | — | +10 to +15 |
| p53 overexpression | Overexpression of wild-type Dmp53 during adult life has no significant effect on lifespan [16303568]. | Fly | — | — | — |
GenAge
GenDR
