|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 .
||Yeast ||+23.1 ||+25.0 ||+34.0 |
|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 . ||Yeast ||+39.3 to +44.8 ||+39.3 to +48.3 ||+50.0 to +60.0 |
|PEP4 overexpression ||Overexpression of vacuolar aspartyl protease (PEP4) extends chronological lifespan by increasing cytosolic polyamine and S-adenosylmethionine (SAM) levels. Deletion of PEP4 results in both apoptotic and necrotic cell death during chronological aging . ||Yeast ||— ||— ||— |
|OSH3 overexpression ||Overexpression of OSH3 with the promoter of VAC8 shortens mean replicative lifespan ad promotes vacuolar fusion [Xia et al. unpublished]. ||Yeast ||— ||— ||— |
|BMH2 overexpression ||Overexpressing 14-3-3 protein, Bmh2, significantly extends median chronological lifespan by activating stress response . ||Yeast ||— ||— ||— |
|YDC1 overexpression ||YDC1 overexpression decreases chronological lifespan by 40% . ||Yeast ||-40 ||— ||— |
|MXR2 overexpression ||Overexpression of MXR2 (alias MsrB) has no effect on replicative lifespan under normal growth conditions, but under DR conditions extends replicative lifespan by 120% . ||Yeast ||— ||— ||— |
|MXR1 overexpression ||Overexpression of MXR1 (alias MsrA) slightly increases the replicative lifespan .
||Yeast ||— ||— ||— |
|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 . ||Yeast ||— ||+24 ||— |
|CTA1 overexpression ||CTA1 overexpression partially suppresses the shortened chronological lifespan by ISC1 mutation . ||Yeast ||— ||— ||— |
|FBP1 overexpression ||Overexpression of FBP1 shortens chronological lifespan . ||Yeast ||— ||— ||— |
|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) . ||Yeast ||— ||— ||— |
|AAT1 overexpression ||Overexpression of AAT1 extends replicative lifespan by 25% and does not synergize with 0.5% glucose restriction . ||Yeast ||+25 ||— ||— |
|GUT2 overexpression ||Overexpression of GUT2 extends replicative lifespan by 25% and does not synergize with 0.5% glucose restriction . ||Yeast ||+25 ||— ||— |
|HST2 overexpression ||HST2 overexpression extends replicative lifespan. 0.5% glucose restriction does not increase lifespan of sir2;fob1;hst2 triple mutants . DR increases lifespan of all four sir2;fob1;hstX(X = sirtuin) triple mutants [16741098; 17129213]. ||Yeast ||— ||— ||— |
|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 . 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 ||— ||— |
|MDH1 overexpression ||Overexpression of MDH1 extends replicative lifespan by 25% and does not synergize with 0.5% glucose restriction . ||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 . ||Yeast ||+20 to +25 ||— ||— |
|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 . ||Yeast ||— ||— ||— |
|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 ||— ||— ||— |
|FRE6 deletion ||FRE6 deletion increases mean replicative lifespan by 14% and cancels out the lifespan extending effect of DR . ||Yeast ||+14 ||— ||-2 |
|Elevation of histone expression ||The elevation of histone expression promotes replicative lifespan extension . ||Yeast ||— ||— ||— |
|IME1 transient overexpression ||Transient overexpression of IME1 resets the replicative lifespan of old cells back to that of young cells . ||Yeast ||— ||— ||— |
|NDT80 transient overexpression ||Transient overexpression of NDT80 rejuvenates old cells . ||Yeast ||— ||— ||— |
|SSD1-V overexpression ||Overexpression of SSD1 (addition of a SSD1-V allele) increases replicative lifespan by 50%, independently of SIR2 and SIR2 further extends the lifespan, although SIR2 is necessary for SSD1-V cells to attain maximal lifespan . SSD1-V also dramatically increases chronological lifespan with lifespan twice as long as ssd1-d cells .
Addition of SSD1-V allele to an ssd1-d strain suppresses the short lifespan of an MPT5 deletion mutant  and extend wild-type lifespan [Kaeberlein and Guarente, unpublished].
SSD1-V slightly extends the lifespan of swi4 and ccr4 mutant strains and suppresses the temperature sensitive growth phenotype of mpt5, ccr3, swi4, and swi6 single mutants . SSD1-V also suppresses the synthetic lethality caused by deletion of MPT5 in combination with a mutation in SWI4, SWI6, or CCR4 . SSD1-V suppresses mutations that affect cell wall stability [1545797; 8386319], RNA polymerase III activity , RNA splicing , and PKA activity [1848673; 8200529]. ||Yeast ||+50 to +100 ||— ||— |