| Sin3A overexpression | Overexpression of Sin3A increases mean and maximum lifespan by 13% and 3%, respectively [22366109]. | Fly | +13 | — | +3 |
| SIFR overexpression | Overexpression of SIFR in males extends mean and maximum lifespan by 23% and 3%, respectively [22366109]. | Fly | +23 | — | +3 |
| hsf-1 overexpression | Overexpression of hsf-1 extends the mean, median, and maximum lifespan by 37, 35, and 29% [22737090]. | Worm | +37 | +35 | +29 |
| ucp2 overexpression | Overexpression of ucp2 increases mean, median, and maximum lifespan by 42, 40, and 26%, which is non-additive with sDR [22737090]. | Worm | +42 | +40 | +26 |
| lys-1 overexpression | Overexpression of lys-1 increases mean and maximum lifespan by 5 and 26%, but has no significant effect on median lifespan [22737090]. | Worm | +5 | — | +26 |
| CG10916 overexpression | Overexpression of CG10916 in males increases mean and maximum lifespan by 27% and 26%, respectively [22366109]. | Fly | +27 | — | +26 |
| hep overexpression | Overexpression of hey significantly extends median (50%) and maximum (25%) lifespan [14602080]. | Fly | — | +50 | +25 |
| aak-2 overexpression | Transgenic animals with a higher aak-2 gene dose live on average 13% longer with a maximum lifespan extension on up to 25% [15574588]. | Worm | +13 | — | +25 |
| PGRP-LF overexpression | Overexpression of PGRP-LF increases mean and maximum lifespan by 13% and 24% [22366109]. | Fly | +13 | — | +24 |
| NNT1 overexpression | Overexpression of NNT1 by 5-fold extends mean and maximum replicative lifespan by 18 and 23%, which is approximately of the same magnitude as the lifespan extension obtained from DR.DR in NNT1 overexpression mutant fails to significantly affect the lifespan and only results in extended mean lifespan by 12% and reduced maximum lifespan by 11%. NNT1 overxpression increases rDNA silencing [12736687]. | Yeast | +18 | — | +23 |
| 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 |
| TXN overexpression | Overexpression of TXN1 in transgenic C57BL/6 mice resulted in extended median (35%) and maximum (22%) lifespan. Telomerase activity in spleen tissues of TXN1 overexpressing mice is higher than tha in wild-type [12230882]. | Mouse | — | +35 | +22 |
| Bub1b overexpression | Sustained high-level expression of BubR1 preserves genomic integrity and reduces tumorgenesis (even in the presence of genetic alterations that strongly promote aneuplodization and cancer, such as oncogenic Ras) and extends the lifespan and delays age-related deterioriation and aneuploidy in several tissues [23242215].
BubR1 overabundance exerts its protective effect by correcting mitotic checkpoints defects [23242215].
BubB1 overexpression extends maximum lifespan by 20 - 41% compared to GFP-carrying control transgenic mice [23242215]. | Mouse | — | — | +20 to +41.3 |
| Eip71CD overexpression | Overexpression of Eip71CD (alias MsrA) in nervous system extends the lifespan by up to 70%, increases resistance to oxidative stress, and delays the onset of senescence-induced decline in activity levels and reproductive capacity. Eip71CD is a downstream effector of foxo [22310715].
Mean and maximum lifespan is increased by up to 2-% in animals that overexpress Eip71CD [20655917]. | Fly | +20 to 70 | — | +20 |
| Sod2 overexpression | Overexpression of Sod2 by 5-115% decreases lifespan by 4-5% without any compensatory changes in metablic rate, level of physical activity, or the levels of other antioxidants (Sod, Cat, and glutathione) [10545213]. Targeted overexpression of Sod2 in motor neurons alone extends lifespan by 30% [11113599]. Induced overexpression of Sod2 in adult animals extends lifespan up to 37% [12072463]. Overexpression of catalase in combination with SOD2 has no added benefit for lifespan [12072463]. Animals overexpressing SOD2 or catalase do not exhibit a decrease in metabolism as measured by oxgen consumption [12072463].
Sod2 overexpression results in a 20% increase in mean and maximum lifespan [18067683]. | Fly | +20 to +37 | — | +20 |
| SNCA overexpression | Transgenic lines overexpressing either human wild-type or mutant (A53T) forms of the SNCA (alpha-synclein) gene under a pan-neuronal promoter live on average about 25% longer, even in weak (m577) and strong (e1370) daf-2 mutant backgrounds, and exhibited decreased pharyngeal pumping and egg-laying. Wild-type SNCA crossed into eat-2(ad1113) does not significantly effect lifespan compared to that of the background strain. Pumping rate in wild-type SCNA and A53T SCNA overexpression mutants were less than control already at day 1 of adulthood. The attenuation of lifespan exptesion by SNCA overexpression by growing on thick bacterial lawns, suggests that DR may explain some fo the effects on lifespan. SCNA overexpression increases average lifespan by 21.3% (wild-type) and 16.3% (A53T) [16782295]. | Worm | +26 to +34 | — | +19 to +31 |
| RAS2 overexpression | Overexpression of RAS2 causes a 43% increase in mean and 18% increase in maximum lifespan as well as postpones the age-related increase in generation time [8034612]. | Yeast | +43 | — | +18 |
| 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 |
| Overexpression of mitochondrial targeted CAT | Overexpression of human catalase targeted to mitochondria (MCAT) extends mean and maximum lifespan by about 20% in mice. Inactivation of aconitase in heat mitochondria and mitochondrial damage is also reduced in long-lived CAT mutant mice [15879174].
The MCAT strain has a reduced severity of age-dependent arteriosclerosis and increased genomic stability, as indicated by an decrease in oxidative stress and mitochondrial deletions in heart and muscle tissues. Median and maximum lifespan in increased about 17 - 21% [16144468]. | Mouse | +20 | +17 to +21 | +17 to +21 |
| 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 |
| 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 |
| Sirt6 overexpression | Overexpression of Sirt6 in male mice lengthens the median lifespan by 9.9-14.5% and maximum lifespan by 13.1-15.8% [22367546]. | Mouse | — | +9.9 to +14.5 | +13.1 to +15.8 |
| to overexpression | Overexpression of to adult neurons, pericerbral or abdonimal fat body increases male and female lifespan. to overexpression in the adult nervous system, head fat body and abdominal fat body results in 25, 20 and 12-18% increase of mean lifespan. on average the mean lifesapn is extended for males and females by 18 and 26%, while maximum lifespan of male and female is increased by 13 and 25% [20519778]. | Fly | +12 to +26 | — | +13 to +25 |
| 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 |
| 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 |
GenAge
GenDR
