| 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 | — | — |
| 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]. | — | — | — | — |
| Klotho overexpression | Klotho overexpression leads to lifespan extension [16123266]. | Mouse | — | — | — |
| ImpL2 overexpression | Lmp-L2 over-expression, ubiquitous or restricted to DILP-producing cells and/or gut and fat body, extends lifespan even if induced at adult onset [21108726]. Overexpression of ImpL2 increases mean and maximum lifespan by 15% and 23%, respectively. Lifespan is reduced when Impl2 is strongly over-expressed throughout the adult by the conditional GS driver, act-GS-GAL4 or da-GS-Gal3, while restricted over-expression of the ImpL2 in fat cells by using S106-GS-Gal4, which increases mRNA level about 6-fold extends lifespan in both sexes [22366109]. mRNA for Impl2 was strongly elevated in sterile, long-lived flies [18434551]. | Fly | +15 | — | +23 |
| Lamp2a expression restoration | Maintaining the amount of the Lamp2a (in a double transgenic mice) specifically in the liver at levels found in young adults prevents age-dependent decrease in receptor abundance at the cellular and organ levels. In this mice CMA activity is maintained until advanced ages which results in preservation of the autophagic activity and is associated with lower intracellular accumulation of damaged proteins, better ability to handle protein damage and improved organ function [19115216; 18690243]. Lamp2a expression restored not only CMA but also macrophagy and proteasomal degradation to the level observed in young liver as well as youthful mitochondrial function and cellular ATP abundance and overall youthful liver functions [18776878]. | Mouse | — | — | — |
| Zw overexpression | Mean lifespan of G6PD overexpressor flies is extended in comparison with driver and responder controls, armadillo-GAL4 (up to 38%), Tubulin-GAL4 (up to 29%), C23-GAL4 (up to 27%), da-GAL4 (up to 24%), D42-GAL4 (up to 18%) and Appl-GAL4 (up to 16%). The maximum lifespan is also increased [18809674].
G6PD enzymatic activity as well as levels of NADPH, NADH, and the GSH/GSSG ration are increased [18809674]. | Fly | +16 to + 38 | — | — |
| Tert overexpression | Mice genetically modified to express telomerase lived 40% longer and do not develop cancer. Overexpression of Tert in mice engineered to be cancer-resistant by means of ehanced expression of p53, p16 and p19ARF (Sp53/Sp16/SARF/TgTERT) decreased telomere shortening with age, delayed aging and increases mean and median longevity by 40% [19013273]. | Mouse | +40 | +40 | — |
| Heterozyogus Trp53 truncation mutation | Mice heterozyogous for an allele of p53 that removes the 5' portion of the protein demonstrate decreased cancer, permature aging phenotypes, and shortened lifespan in the mixed inbred C57BL/6â129/Sv background. It has been proposed that the this allele of p53 results in increased activity/overexpression [11780111]. | Mouse | — | — | — |
| Tert gene therapy | Mice treated with an adeno-assoicated virus vector expressing TERT at the age of one lived 24% longer on average and those treated at the age of two, by 13%. Maximum lifespan of the mice treated at 1 and 2 years was also extended by and 13% and 20%, respectively. AAV9-mTERT treated mice also had improved health, delayed onset of age-related diseases (like osteoporosis and insulin resistance) as well as improved readings in ageing indicators like neuromuscular coordination [22585399].
The gene therapy consists of a single injected via tail vein and achieved a transduction efficiency of 20-50%. Already 1 month after treatment, the treated mice at both age groups had longer telomeres and a decrease in the short telomeres in multiple tissues, while the controls exhibit an increase in short telomerase. In contrast to their control littermates at 3 and 8 months post-treatment the blood of most of the AAV9-treated mice at 1 year had no decrease or exhibit even a net increase in average telomere length and had also no increase or even a marked decrease in percentage of short telomeres with time. Thus, the therapy achieved in perhipheral blood leukocytes a prevention of telomere shortening. Treated mice had lower leves of fasting insulin, improved glucose tolerance and better homeostatic model assessment. Two years old treated mice had higher IGF1 levels. Treated mice at both ages had improved memory scores. AAV9-mTERT treatment increased cyclinD1 positive cells in various tissues. Upon AAV9-mTERT treatment levels of p16 decreased in most organs (with exception of heart). The metabolic and mitochondrial decline in 2 years old mice treated was not as apparent as in controls [22585399].
| Mouse | +13 to +24 | — | +13 to +20 |
| mir-246 overexpression | mir-246 overexpression increases mean and maximum lifespan by 6 and 5 - 14%, respectively [21129974]. | Worm | +6.3 | — | +4.8 to +14.3 |
| MTF-1 overexpression | MTF-1 overexpression in either the peripheral nervous system or motorneurons extends both mean and maximum lifespan by 40% in males [18775584]. | Fly | +40 | — | +40 |
GenAge
GenDR
