Interventions

  • name effect species mean median maximum
    VhaSFD overexpression Overexpression of VhaSFD (from a doxycycline-inducible promoter) results in a 5-10% increase in mean lifespan [12620118]. Fly +5 to +10
    IME1 transient overexpression Transient overexpression of IME1 resets the replicative lifespan of old cells back to that of young cells [21700873]. Yeast
    NDT80 transient overexpression Transient overexpression of NDT80 rejuvenates old cells [21700873]. Yeast
    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
    Gh antagonist overexpression Overexpression of a growth hormone antagonist (a mutated bovine growth hormone that competes with the endogenous one) has no effect on lifespan [12933651]. Mouse
    uba-1 overexpression Overexpression of uba-1 does not result in significant increase in median lifespan [22737090]. Worm
    Mir20a Overexpression Overexpression of MiR-20a in mouse embryonic fibroblasts induces senescence by lowering Lrf (a transcriptional repressor of the Mdm2 inhibitor p19ARF [15662416; 9529248]) protein levels and in turn increasing p19ARF levels [18596985]. Mouse
    Trxr-1 overexpression Overexpression of Trxr-1 (alias GSR; glutathione reductase) in transgenic flies results in increased lifespan and oxidative stress resistance, but only under hyperoxia [10506576]. Fly
    pnc-1 overexpression Overexpression of pnc-1 increases adult survival under oxidative stress but does not extend the lifespan [17335870]. Worm
    atf1 overexpression Overexpressing atf1 is not sufficient to promote chronological lifespan extension in cells lacking sty1 [20075862].
    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and this effect was overlapping with moderate DR, because DR can not extend the lifespan of this mutant [Tang et al., unpublished].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
    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
    MDH1 overexpression Overexpression of MDH1 extends replicative lifespan by 25% and does not synergize with 0.5% glucose restriction [18381895]. Yeast +25
    NDE1 NDE2 overexpression Overexpression of NDE1 and NDE2 increases intracellular NAD/NADH ratio by lowering NADH concentration and increases replicative lifespan by 20-25%. This lifespan extension is non-additive with 0.5% glucose restriction [14724176]. Yeast +20 to +25
    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
    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
    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
    GUT2 overexpression Overexpression of GUT2 extends replicative lifespan by 25% and does not synergize with 0.5% glucose restriction [18381895]. Yeast +25
    AAT1 overexpression Overexpression of AAT1 extends replicative lifespan by 25% and does not synergize with 0.5% glucose restriction [18381895]. Yeast +25
    Overexpression of ucp2 and aakg-2 Overexpression of aakg-2 toegther with D. rerio ucp2 was non-additive with sDR [22737090]. Worm
    ubc-18 overexpression ubc-18 overexpression is unable to extend lifespan (possibly, UBC-18 is not limiting for WWP-1 function in lifespan) [19553937]. Worm
    aqp-1 overexpression Overexpression of aqp-1::GFP rescues short lifespan of aqp-1 deletion mutants and partially prevented glucose from shortening lifespan. Worm
    cbp-1 overxpression Overexpression of cbp-1 does not significantly affect lifespan [19924292]. Worm
    trx-1 overexpression trx-1 overexpression extends lifespan in wild-type but not in eat-2 mutants. Ectopic expression of trx-1 in ASJ neurons (but not in the intestine) in trx-1 mutants rescues the lifespan-extension conferred by eat-2 mutation. trx-1 overexpression extends lifespan of wild-type but not in eat-2 mutants. trx-1 deletion almost completely suppresses lifespan extension induced by dietary deprivation (DD). DD upregulates trx-1 expression in ASJ neurons. DR activates trx-1 in ASJ neurons which in turn triggers a trx-1-dependent non-cell autonomous mechanism to extend adult lifespan [21334311]. Worm
    wwp-1 overexpression wwp-1 overexpression extends lifespan by up to 20%. RNAi reduction of pha-4, but not of daf-16 suppresses increased longevity by wwp-1 overexpression [19553937]. Worm +20
    Interventions are an extension of GenAge and GenDR.