| Cisd2 overexpression | A persistent level of Cisd2 achieved by transgenic expression extends mean, median and maximum lifespan without any apparent deleterious side effects [22661501]. | Mouse | — | — | — |
| 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 | — | — |
| magu overexpression | Adult-specific overexpression of magu increases lifespan by 5-30% and modulates late-age fecundity [19011900]. | Fly | +5 to +30 | — | — |
| 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 | — |
| SGS101 antisense RNAi | Antisense RNA interference of SAG101 in transgenic plants delays the onset of leaf senescence for approximately 4 days [11971136]. | — | — | — | — |
| Atg2 overexpression | Atg2 overexpression increases average female lifespan by 28% [18059160]. | Fly | +28 | — | — |
| Igf1 overexpression | Cardiac specific overexpression of Igf1 results in a 23% increase in median lifespan, though no increase in maximum lifespan [17973971]. | Fly | — | +23 | — |
| PNC1 overexpression | Cells with 5 copies of PNC1 have a 70% longer replicative lifespan which is cancelled out by SIR2 deletion. Overexpression of PNC1 suppresses the effect of exogenously added nicotinamide on Sir2-dependent silencing at HM loci, telomeres and rDNA loci [12736687; 14729974]. PNC1 overexpression suppresses the inhibitory effect of exogenously added NAM on silencing, lifespan, and Hst1-mediated transcriptional repression [14729974]. Increased expression of PNC1 is both necessary and sufficient for replicative lifespan extension by DR and low-intensity stress. Under non-stressing conditions (2% glucose, 30 degree Celsius), a strain with additional copies of PNC1 (5XPNC1) has 70% longer replicative lifespan than the wild-type and some cells live for more than 70 divisions. Neither DR nor heat stress further increase the lifespan of the 5XPNC1 strain [12736687]. | Yeast | +70 | — | — |
| SGS101 chemical induced overexpression | Chemical induced overexpression of SAG101 causes precocious senescence in both attached and detached leaves of transgenic plants [11971136]. | — | — | — | — |
| SOD2 overexpression | Combined overexpression of SOD1 and SOD2 extends chronological lifespan by 30% in EG103 strain [12586694].
| Yeast | — | — | — |
| Constitutive miR-277 expression | Constitutive miR-277 expression shortens lifespan and synthetically lethal with reduced insulin signaling, indicating that metabolic control underlies this phenotype [23669073]. | Fly | — | — | — |
| CTA1 overexpression | CTA1 overexpression partially suppresses the shortened chronological lifespan by ISC1 mutation [21707788]. | Yeast | — | — | — |
| cup-4 overexpression | cup-4 overexpession reduces oxidative stress resistance and shortens lifespan of wild-type under AL [19783783]. | Worm | — | — | — |
| Hsp22 doxycyline-regulated overexpression | Doxycyline-regulated overexpression of Hsp22 makes animals more sensitive to heat and oxidative stress as well as reduces the mean lifespan by up to 21%, particularly at higher culture temperature [15491684].
| — | -21 | — | — |
| HES1 overexpression | Elevation of HES1 levels by an ERG6 promoter reduces mean, median and maximum replicative lifespan by 25, 18 and 29% [Geber et al., unpublished] | Yeast | -25 | -18 | -29 |
| OSH6 overexpression | Elevation of OSH6 levels by an ERG6 promoter extends mean, median and maximum replicative lifespan by 39, 52 and 18% which is non-additive with 0.5% glucose restriction. It also extends the lifespan of NYV1 mutant [Geber et al., unpublished].
The long lifespan of Perg6-OSH6 is not further extended by deletion of TOR1 [22622083].
OSH6 overexpression decreases total cellular sterol content and reduces Lst8 protein levels. The CC domain of Osh6 is dispensable for longevity [Fusheng Tang, personal communication]. | Yeast | +39 | +52 | +18 |
| Atg8a overexpression | Enhanced expression of Atg8a in older fly brains extends average adult lifespan by 56% and promotes resistance to oxidative stress [18059160]. | Fly | +56 | — | — |
| 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 |
| INS overexpression | Expression of human insulin under an inducible heat shock promoter increases nematode lifespan by 25% and is also able to enhance the lifespan of daf-2 mutants [11274053]. | Worm | +25 | — | — |
| 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 | — | — | — |
| 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 | — |
| faah-1 overexpression | faah-1 overexpression reduces eicosapentaenoyl ethanolamide (EPEA), palmitoleyol ethanolamide, linoleyol ethanolamide, as well as arachidonoyl ethanolamide (AEA) levels, delays development, increases thermal stress resistance, and was associated with mean and maximum adult lifespan extension by 19 and 35%, respectively, in presence of abundant food but not under (two different protocols of) DR. Overexpression in pharynx was largely sufficient for this lifespan extension [21562563]. | Worm | +19 | — | +35 |
| rpr overexpression | Flies with ablated wings caused by overexpressing reaper (UAS-rpr) with a wing-specific Gal4 enhancer trap (1096-Gal4) exhibit only a 14% extension in lifespan compared to controls which exhibit a 61% extension upon DR [22768842]. | Fly | — | — | — |
| 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 | — |
| 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 | — | — | — |
GenAge
GenDR
