| fh overexpression | Overexpression of fh in the mitochondria of female transgenic animals increases antioxidant capability, resistance to oxidative stress insults, and longevity [18258192]. | Fly | — | — | — |
| 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 | — | — | — |
| 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 | — |
| FPS1S overexpression | Plants overexpressing FPS1S exhibit a cell death/senescence-like phenotype and grw vigorously than wild-type [12000449]. In plants with increased FPS activity, the expression of senescence activated gene SAG12 is prematurely induced. | — | — | — | — |
| 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 | — | — | — |
| Gclc overexpression | Overexpression of Gclc extended mean and maximum lifespan by up to 50% [16148000]. | Fly | +50 | — | +50 |
| Gclm overexpression | Overexpression of Gclm extends the mean lifespan by up to 24% [16148000]. | Fly | +24 | — | — |
| GH overexpression | Overexpression of GH is associated wtih markedly reduced lifespan and various indices of premature aging [8100276]. Transgenic mice overexpressing bovine Gh1 are bigger than controls and display early onset of pathological changes in the kidneys such glomerulosis and glomerulonephritis as well as signs of premature aging such as a shortened lifespan, increased astrogliosis, shortened reproductive lifepsan and early onset of age-related changes in cognitive function, hypothalamic neurotransmitter turnover, and plasma corticosterone levels [14583653]. | Mouse | — | — | — |
| 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 | — | — |
| gig overexpression | Overexpression of gig, also known as dTsc2, results in lifespan extension. Overexpression of dTsc2 increases mean lifespan by 20% and 12%, at 25°C and 29°C, respectively, and protects from deleterious effects of rich food, as if mimicking the effect of DR [15186745].
Overexpression of dTsc2 via a UAS promoter in the eye using the driver gmr-GAL4 or in the nervous system by using appI-GAL4 does not extend the lifespan. Using the drivers 24BGAL4 and PO188-GAL4, enhancer traps that are predominantly expressed in the muscle and fat results in mean lifespan extension of 27% and 37%, respectively, at 29°C [15186745]. Fat-specific drivers DJ634-GAL4 and PO163-GAL4 when used to overexpress dTsc2, also led to a mean lifespan extension of 22% and 31%, respectively, at 29°C [15186745]. | Fly | +20 to +31 | — | — |
| git3 constitutive activative mutation | Constitutive activation of the G-alpha subunit acting downstream of Git3 accelerates aging and inhibits the effect of DR [19266076]. | | — | — | — |
| 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 | — | — |
| gpa2 constitutive active mutation | Constitutive active mutation of gpa2 (alias git8) decreases chronological lifespan under AL (2% glucose) and almost completely cancels out the lifespan extending effect of DR (0.2% glucose) [19266076]. | | — | — | — |
| Gr63a overexpression | Overexpression of Gr63a has modest negative effect on lifespan [20422037]. | Fly | — | — | — |
| GstS1 overexpression | GstS1 overexpression increases the mean lifespan by 33% [18059160]. | Fly | +33 | — | — |
| GUT2 overexpression | Overexpression of GUT2 extends replicative lifespan by 25% and does not synergize with 0.5% glucose restriction [18381895]. | Yeast | +25 | — | — |
| HAP4 overexpression | Overexpression of HAP4 from the ADH1 promoter extends lifespan of PSY316 strain approximately 40% under growth conditions favoring fermentation (2% glucose). Overexpression of HAP4 increases replicative lifespan, but is non-additive with 0.5% glucose restriction in lifespan extension. Lifespan extension by HAP4 overexpression requires SIR2 [12124627]. HAP4 deletion suppresses replicative lifespan extension to 30% and 33% on 0.1% glucose and on elimination of non-essential amino acids, respectively [20178842]. HAP4 overexpressing cells demonstrate a transcriptional response resembling cells undergoing diauxic shift, consume more oxygen, and exhibit increased Sir2-dependent transcriptional silencing at telomeres and rDNA [12124627]. | Yeast | +30 to +40 | — | — |
| 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 | — | — |
| hep overexpression | Overexpression of hey significantly extends median (50%) and maximum (25%) lifespan [14602080]. | Fly | — | +50 | +25 |
| 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 |
| 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 | — | — | — |
| Hsc70-3 overexpression | Overexpression of Hsc70-3 increases average female lifespan by 27% [18059160]. | Fly | +27 | — | — |
| hsf-1 overexpression | Overexpression of hsf-1 extends the mean, median, and maximum lifespan by 37, 35, and 29% [22737090]. | Worm | +37 | +35 | +29 |
| hsp-16 overexpression | Overexpression of the hsp-16 loci enhances stress resistance and extends mean lifespan by 11% at 20 degree Celsius. Lifespan extension by hsp-16 overexpression requires daf-16 [12882326]. | Worm | +11 | — | — |
GenAge
GenDR
