Interventions

  • name effect species mean median maximum
    CLN3 overexpression Overexpression shortens chronological lifespan together with age-dependent increases in genome instability and apoptosis. While around 80% of wild-type cells are alive almost non CLN3 overexpressers are alive (under condition that avoids adaptive regrowth) [17710147]. Yeast
    Constitutive active S6k overexpression Overexpression of a constitutively active form of S6k (alias dS6K) decreases mean lifespan by 34% at 29°C [15186745]. Fly -34
    Constitutive miR-277 expression Constitutive miR-277 expression shortens lifespan and synthetically lethal with reduced insulin signaling, indicating that metabolic control underlies this phenotype [23669073]. Fly
    Coq7 overexpression Transgenic overexpression of mouse Coq7 reverts the extended lifespan of clk-1 mutants [11511092]. Worm
    cst-1 overexpression Overexpression of cst-1 extends lifespan and delays aging in a daf-16-dependent manner [16751106]. Worm
    CTA1 overexpression CTA1 overexpression partially suppresses the shortened chronological lifespan by ISC1 mutation [21707788]. Yeast
    cup-4 overexpression cup-4 overexpession reduces oxidative stress resistance and shortens lifespan of wild-type under AL [19783783]. Worm
    daf-16 overexpression Overexpression of wild-type DAF-16 modestly increases lifespan by 20% [11747825]. Worm +20
    daf-18 overexpression Overexpression increases adult lifespan in individual tissues [16153634]. Worm
    DNApol-gamma35 overexpression Overexpression of DNApol-gamma35 (DNA polymerase gamma) in the nervous system results in a decrease in the median lifespan ranging from 39% to 52% [17999718]. Fly -39 to -52
    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
    Dominant-negative S6k Ubiquitous overexpression of a dominant-negative form of S6k (alias dS6K) increases mean lifespan by 22%. Overexpression of a dominant-negative form of S6k protects mutants from deleterious effects of rich food, as if mimicking the effect of DR [15186745]. Fly +22
    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
    Ef1alpha48D overexpression Overexpression of Ef1alpha48D (transformed with a P-element vector and under control of hsp70 regulatory sequences) results in lifespan extension by 18-41% [2508089]. Fly +18 to +41
    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
    ERG2 overexpression Overexpression of ERG2 with the promoter of ERG6 (Perg6-ERG2) extends replicative lifespan and this effect was overlapping with moderate DR, because DR can not extend the lifespan of this mutant [Tang et al., unpublished]. Yeast
    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
    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
    FBP1 overexpression Overexpression of FBP1 shortens chronological lifespan [16199065]. Yeast
    Fgf21 overexpression Overexpression of Fgf-21 increases the mean lifespan by 30% for male mice and 39% for female mice [23066506]. Mice overproducing Fgf21 are lean throughout their lives and remain lean even while eating slightly more than wild-type mice. Fgf21 overproducers tend to be smaller than wild-type mice and female mice were infertile. Although Fgf21 overproducers have significantly lower bone density than wild-type, Fgf21-abundant mice exhibit no ill effects from the reduced bone density and remain active into old age without any broken bones [23066506]. Mouse +30 to +39
    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.
    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
    Interventions are an extension of GenAge and GenDR.