| 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 | — |
| FRE6 deletion | FRE6 deletion increases mean replicative lifespan by 14% and cancels out the lifespan extending effect of DR [22912585]. | Yeast | +14 | — | -2 |
| 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 | — | — | — |
| mir-71 overexpression | Gain-of-function of mir-71 increases lifespan [21129974]. Extra copies of mir-71 extend the lifespan with an increase in lifespan by 15 - 25% [22482727], | Worm | +15 to +25 | — | — |
| Ghr knockout | Ghr knockouts (the so called Laron mice) are dwarfs with significantly extended lifespan by 40-50% [12933651]. Ghr-/- mice are significantly longer lived as Ghr+/+ or Ghr+/- mice (by 40-50%) in both females and males [10875265; 19370397]. 30% DR fails to affect overall survival, average or median long-lifespan of Growth hormone receptor knockout (GHRKO) mice and increased maximal lifespan only in females. Insulin sensitivity in GHRKO mutants is greater than in wild-type and is not further increased by DR [16682650]. Intermittent fasting also fails to extend the long lifespan of GHRKO mice [19747233].
Lifespan of mice with a deletion in the Ghr gene live almost 5 years [21123740]. In C57BL/6J this mutation increases life expectancy by 16 to 26% depending on gender [12933651] and in mice of mixed genetic background the increases amounted to 36-55% [9371826]. Serum levels of GH are elevated in mutant mice [9371826] and mutants are smaller than wild-type. IGF-1 and IGFBP-3 levels are also reduced in Ghr mutant mice [10875265]. The age-associated decline in memory retention is delayed in Ghr mutants [11336996]. | Mouse | +16 to +55 | — | — |
| GstS1 overexpression | GstS1 overexpression increases the mean lifespan by 33% [18059160]. | Fly | +33 | — | — |
| Nudt1 Overexpression | hMTH1-Tg mice express high levels of the hMTH1 hydrolase that degrades 8-oxoGTP and 8-oxoGTP and excludess 8-oxoguanine from both DNA and RNA.
hMTH1-overexpresing mice have significantly lower steady-state levels of 8-oxoguanine in both nuclear and mitochondrial DNA of several organs, including the brain. hMTH1 overexpression prevents the age-dependent accumulation of DNA 8-oxoguanine that occurs in the wild-type mice. These lower levels of oxidized guanines are associated with increased longevity and hMTH1-Tg animals live significantly longer than their wild-type littermates [23648059]. | Mouse | — | — | — |
| Hsp22-promoter driven reporter overexpression | Hsp22-promoter driven reporter overexpression reduces mean and maximum lifespan [19420297]. | Fly | — | — | — |
| Hsp70Ba overexpression | Hsp70Ba overexpression reduces mean and maximum lifespan up to 30% [19420297]. | Fly | -30 | — | -30 |
| HST2 overexpression | HST2 overexpression extends replicative lifespan. 0.5% glucose restriction does not increase lifespan of sir2;fob1;hst2 triple mutants [16051752]. DR increases lifespan of all four sir2;fob1;hstX(X = sirtuin) triple mutants [16741098; 17129213]. | Yeast | — | — | — |
| LAT1 overexpression | In contrast, overexpressing LAT1 extends replicative lifespan, and this lifespan extension was not further increased by 0.5% glucose restriction. Similar to DR, replicative lifespan extension by LAT1 overexpression largely requires mitochondrial respiration [17200108]. Overexpressing Lat1 extends lifespan (20% mean lifespan increase) and this lifespan extension is not further increased by DR. Similar to DR, lifespan extension by LAT1 overexpression largely requires mitochondrial respiration indicating mitochondrial metabolism plays an important role in DR. Interestingly, LAT1 overexpression does not require the Sir2 family to extend lifespan. Lat1 is also a limiting longevity factor in non-dividing cells in that overexpressing LAT1 extends cell survival during prolonged culture at stationary phase. | Yeast | +20 | — | — |
| ins-1 overexpression | Increased dosage of ins-1 under its own promoter as well as a heat shock promoter increases lifespan by 25% and is also able to increase the lifespan of daf-2 mutants. Overexpression of ins-1 also causes an increase in dauer formation and can enhance the dauer formation of daf-2 mutants [11274053]. | Worm | +25 | — | — |
| NPT1 overexpression | Increased dosage of NPT1 increases SIR2-dependent silencing, stabilizes the rDNA locus and extends replicative lifespan by up to 60%. 0.5% glucose restriction does not significantly further increase replicative lifespan of NPT1 overexpression [11884393]. NPT1 deletion decreases replicative lifespan by 50% [17482543] as well as chronological lifespan [17110466]. Deletion of NPT1 shortens the lifespan in W303R. Replicative lifespan extension of cdc25-10 mutation (assumed to act as a genetic DR-mimetic) is cancelled out by NPT1 deletion [11000115]. | Yeast | +60 | — | — |
| Foxm1 overexpression | Increased hepatocyte expression in 12-month-old (aged) transgenic mice of Foxm1b alone is sufficient to restore hepatocyte proliferation to levels found in 2-month-old (young) regenerating liver [14647066]. | Mouse | — | — | — |
| Pten overexpression | Increased Pten and 4E-BP activity in muscles is extends the lifespan [21111239]. | Fly | — | — | — |
| Pten overexpression | Increasing gene dosage via homogeneous and moderate overexpression, while retaining its normal pattern of tissue expression of Pten increases mean, median and maximum lifespan in both females and males. Mean lifespan is extended by 18% (males), 11% (females) and 14% (both). Median lifespan in males, females and both increases by 12%, 16% and 12%, respectively [22405073]. Transgenic Pten mice carrying the additional genomic copies of Pten are protected from cancer and present a significant extension of lifespan that is independent of their lower cancer incidence. Pten(g) mice have an increased energy expenditure and protection from metabolic pathologies [22405073]. | Mouse | +14 | +12 | — |
| Down syndrom | Individuals with Down syndrome develop the neuropathological lesions of Alzheimer disease significantly earlier than those without [3158266] and have a shorter lifespan. Down syndrome is cuased by duplication of small regions of chromosome 21 [8197171]. The major features of Down syndrome are mental retardation, characteristic facial features, congenital malformations of the heart and gastrointestinal tract, thyroid disease, and an increased incidence of leukaemia [Epstein, 1989]. Neurons cultured in vivo form individuals with Down syndrome degenerate and exhibit apoptosis [8524410]. Down syndrome neurons also display increased generation of reactive oxygen species and treatment with antioxidants can prevent degeneration. | Human | — | — | — |
| Dnmt gene therapy | Injecting a virus that contains extra copies of a Dnmt into elderly mice restored their faulty memories to it oiriganal capacity of young ones. Halving the amount of Dnmt produced by younger mice, deteriotes their memory to that of non-treated older mice [http://www.medicaldaily.com/news/20120702/10573/aging-memory-dna-enzyme-forgetfulness-young-old.htm]. | Mouse | — | — | — |
| SIR2 overexpression | Integration of a second copy of SIR2 into the wild-type strain leads to an extension of replicative lifespan by around 35% in W303R strain[10521401]. 0.05% glucose restriction further extends replicative lifespan of SIR2 overexpression mutant [15328540]. Overexpression extends replicative lifespan in several strains, but not in PSY316 | Yeast | +35 | — | — |
| SAG12 overexpression | Introduction of a SAG12 via bacterial gene transfer (pSAG12:ipt) increases longevity. The gene results in enhanced production of the hormone Cytokinin which affects growth and development as well as stimulates cell division and thereby extends the lifespan. pSAG::ipt transgenic plants exhibit delayed leaf senescence, increased branching and reduced internodal length. The leaves and flowers of the pSAG12:ipt plants are reduced in size and display a more intense coloration [http://www.wissenschaft.de/wissenschaft/news/316062.html; http://www.biomedcentral.com/1471-2229/12/156/abstract; Garcia-Sogo et al. 2012]. | — | — | — | — |
GenAge
GenDR
