| wwp-1 RNAi | RNA interference of wwp-1 decreases median lifespan by 9% in wild-type animals and 24% in daf-2 mutants [18006689]. Loss of wwp-1 function by RNAi reduces lifespan at 25 degree Celsius, but not 20 degree Celsius. Reduced levels of wwp-1 completely suppress the extended longevity of eat-2 mutants. wwp-1 RNAi does not suppress the extended lifespan of isp-1 mutants and has only minor suppressive effects on lifespan of another mitochondrial mutant, clk-1, and in cyc-1 RNAi treated worms. RNAi depletion of wwp-1 has no effect on long lifespan of daf-2 mutants [19553937].
| Worm | — | -9 | — |
| 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HES1 levels by an ERG6 promoter reduces mean, median and maximum replicative lifespan by 25, 18 and 29% [Geber et al., unpublished] | Yeast | -25 | -18 | -29 |
| 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 |
| 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 |
| 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 | — |
| 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 It also extends the lifespan of NYV1 mutant [Geber et al., unpublished].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 |
| hep overexpression | Overexpression of hey significantly extends median (50%) and maximum (25%) lifespan [14602080]. | Fly | — | +50 | +25 |
| aakg-2 overexpression | Overexpression of aakg-2 extends mean, median, and maximum lifespan by 47, 45, and 35% [22737090]. | Worm | +47 | +45 | +35 |
| 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 | — |
| 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 |
| Sir2 overexpression | Overexpression of Sir2 (alias dSir2) extends lifespan by up to 57% and specifically median lifespan by 40-60%. Ubiquitous Sir2 overexpression causes a 4-fold increase in Sir2 mRNA expression and an up to 57% increase in average lifespan (29% for females and 18% for males). A 10 - 20% increase in Sir2 mRNA levels causes no lifespan extension. Neuronal Sir2 overexpression extends average lifespan by 52% in females and 20% in males. Motor-neuronal specific expression fails to cause lifespan extension. DR fails to cause further increase in lifespan or even reduces lifespan toward normal of dSir2 overexpression mutants [15520384]. Mild Sir2 overexpression in the fat-body extends lifespan and reduces relative body fat content in both males and females [22661237].
A diet-dependent lifespan phenotype of dSir2 overexpression in the fat-body, but not in muscles, negates the effects of background genetic mutants [23246004]. | Fly | +18 to + 57 | +4- to +60 | — |
| VMA1 overexpression | Overexpression of VMA1 increases vacuolar acidity and suppresses age-induced mitochondrial dysfunction of aged cells (17 or 18 cell divisions) which requires the V-ATPase activity. VMA1 overexpression significantly increases mean, median and maximum lifespan by 39 - 45%, 39 - 48% and 50 - 60%, respectively. DR (0.5% glucose restriction) does not further increase the lifespan of VMA1 overexpression strain [23172144]. | Yeast | +39.3 to +44.8 | +39.3 to +48.3 | +50.0 to +60.0 |
| 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 |
| lmp-2 overexpression | Overexpression of lmp-2 increases mean, median and, maximum lifespan by 32, 35, and 41% [22737090]. | Worm | +32 | +35 | +41 |
| hsf-1 overexpression | Overexpression of hsf-1 extends the mean, median, and maximum lifespan by 37, 35, and 29% [22737090]. | Worm | +37 | +35 | +29 |
| Akh overexpression | Overexpression of Akh in a ubiquitousness manner enhances fat metabolism (significant increase in triglyceride synthesis and breakdown under AL), spontaneous activity (148% on AL and 154% on DR), and lifespan on AL (33%). However, despite and increase in movement under DR, lifespan is not increased under a restricted diet [22768842]. | Fly | — | +33 | — |
| Spargel overexpression | Tissue-specific overexpression of dPGC-1 in stem and progenitor cells within the digestive tract of females flies extends the median and maximum lifespan of females by up to 33% and 37%. Those mutants display a delay in the onset of aging-related changes in the intestine, leading to improved tissue homoeostasis in old flies [22055505]. | Fly | — | +33 | +37 |
| CG13890 overexpression | Overexpression of CG13890 (DCI) throughout the whole body increases mean and median lifespan by 35 and 31%, but decreases maximum lifespan by 6%, increases stress resistant (to paraquat and starvation), consistently reduces the mortality rate across adult ages and reduces the lifespan extension of DR by 15% [22997544].
CG6783 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 CG6783 [22997544]. | Fly | +35 | +31 | +6 |
| lyz overexpression | Overexpression of lyz increases mean, median, and maximum lifespan by 26, 30 and 44% [22737090]. | Worm | +26 | +30 | +44 |
| 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 | — |
| VPH2 overexpression | Overexpression of VPH2 increases the levels of assembled V-ATPase at the vacuolar membrane, increases vacuolar acidity and suppresses age-induced mitochondrial dysfunction of aged cells (17 or 18 cell divisions) which requires the V-ATPase activity. VPH2 overexpression significantly increases mean, median and maximum replicative lifespan by 23, 25 and 34%, respectively [23172144].
| Yeast | +23.1 | +25.0 | +34.0 |
| sod1 overexpression | Overexpression of sod1 increases mean, median, and maximum lifespan by 21, 25, and 29% [22737090]. | Worm | +23 | +25 | +44 |
| sod-1 overexpression | sod-1 overexpression increases mean, median, and maximum lifespan by 32, 25, and 35% [22737090]. | Worm | +32 | +25 | +35 |
| MAPK1 overexpression | Overexpression of human MAPK1 (alias ERK2) confers resistance to heat shock and oxidative stress extends median chronological lifespan by 24% and was statistically non-addative with cyr1-1 mutation [17662940]. | Yeast | — | +24 | — |
| Jafrac1 overexpression | Neuronal overexpression of Jafrac1 significantly increases both mean and maximum lifespan, while neuronal knockdown as well as loss of function mutation, causes a reduction in lifespan by 30%. The mean lifespan is 26% and 29% higher in females and males, respectively. The maximum lifespan is increased by 22% and 26% in females and males, respectively [19720829].
There is a consistent and significant lifespan extension (15% mean lifespan increase) in both males and females when Jafrac1 is overexpressed in somatic cells. Jafrac1 overexpression using the weaker 5961FS driver moderately but significantly extends lifespan [20976250]. | Fly | +15 to +29 | +22 to +26 | — |
GenAge
GenDR
