| 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 | — | — | — |
| git3 constitutive activative mutation | Constitutive activation of the G-alpha subunit acting downstream of Git3 accelerates aging and inhibits the effect of DR [19266076]. | | — | — | — |
| atf1 overexpression | Overexpressing atf1 is not sufficient to promote chronological lifespan extension in cells lacking sty1 [20075862]. | | — | — | — |
| wis1 constitutive active mutation | Constitutive active mutation of wis1 extends chronological lifespan and there is no further beneficial effect of DR [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and this effect was overlapping with moderate DR, because DR can not extend the lifespan of this mutant [Tang et al., unpublished].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 | — | — | — |
| TSA1 activating mutation | A gain-of-function allele of peroxiredoxin (thioredoxin peroxidase, Tsa1) causes a dominant oxidative stress-resistance and robust premature aging phenotype with reduced mean lifespan. These effect is not provoked by altered Tsa1 levels, nor can it be stimulated by deletion, haploinssufficiency or overexpression of wild-type allele [20729566]. | 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 | — | — | — |
| 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 | — | — | — |
| 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 |
| 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 | — | — | — |
| daf-16 overexpression | Overexpression of wild-type DAF-16 modestly increases lifespan by 20% [11747825]. | Worm | +20 | — | — |
| Overexpression of constitutive nuclear SKN-1 | skn-1 transgenes that overexpress a constitutive nuclear form of SKN-1 in the intestine extend the mean lifespan by 5-21%, independently of DAF-16 [18358814]. | Worm | +5 to +21 | — | — |
GenAge
GenDR
