Interventions

  • name effect species mean median maximum
    sug overexpression Overexpression of sug (from a doxycycline-inducible promoter) results in a 5-9% increase in mean lifespan [12620118]. Fly +5 to +9
    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/6–129/Sv background. It has been proposed that the this allele of p53 results in increased activity/overexpression [11780111]. Mouse
    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
    uba-1 overexpression Overexpression of uba-1 does not result in significant increase in median lifespan [22737090]. Worm
    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
    ucp-4 overexpression Overexpression reduces mean lifespan by 5%, has no significant effect on median lifespan, and slighlty increases maximum lifespan by 12% [22737090]. Worm -5 +12
    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].
    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
    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
    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
    Overexpression of ucp2 and aakg-2 Overexpression of aakg-2 toegther with D. rerio ucp2 was non-additive with sDR [22737090]. Worm
    Interventions are an extension of GenAge and GenDR.