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 |
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 | — | — | — |
FBP1 overexpression | Overexpression of FBP1 shortens chronological lifespan [16199065]. | Yeast | — | — | — |
CTA1 overexpression | CTA1 overexpression partially suppresses the shortened chronological lifespan by ISC1 mutation [21707788]. | Yeast | — | — | — |
MXR1 overexpression | Overexpression of MXR1 (alias MsrA) slightly increases the replicative lifespan [15141092].
| Yeast | — | — | — |
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% [15141092]. | Yeast | — | — | — |
YDC1 overexpression | YDC1 overexpression decreases chronological lifespan by 40% [19059240]. | Yeast | -40 | — | — |
BMH2 overexpression | Overexpressing 14-3-3 protein, Bmh2, significantly extends median chronological lifespan by activating stress response [19805817]. | Yeast | — | — | — |
OSH3 overexpression | Overexpression of OSH3 with the promoter of VAC8 shortens mean replicative lifespan ad promotes vacuolar fusion [Xia et al. unpublished]. | Yeast | — | — | — |
OSH7 overexpression | Overexpression of OSH7 extends mean replicative lifespan. PERG6-OSH7 does not extend the maximum lifespan significantly [Xia et al., unpublished]. | Yeast | — | — | — |
FRE6 deletion | FRE6 deletion increases mean replicative lifespan by 14% and cancels out the lifespan extending effect of DR [22912585]. | Yeast | +14 | — | -2 |
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 [21593793]. | 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 [17662940]. | Yeast | — | +24 | — |
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 [23172144].
| 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 [23172144]. | Yeast | +39.3 to +44.8 | +39.3 to +48.3 | +50.0 to +60.0 |
OSH6 overexpression | Elevation of OSH6 levels by an ERG6 promoter extends mean, median and maximum replicative lifespan by 39, 52 and 18% which is non-additive with 0.5% glucose restriction. It also extends the lifespan of NYV1 mutant [Geber et al., unpublished].
The long lifespan of Perg6-OSH6 is not further extended by deletion of TOR1 [22622083].
OSH6 overexpression decreases total cellular sterol content and reduces Lst8 protein levels. The CC domain of Osh6 is dispensable for longevity [Fusheng Tang, personal communication]. | Yeast | +39 | +52 | +18 |
HES1 overexpression | Elevation of HES1 levels by an ERG6 promoter reduces mean, median and maximum replicative lifespan by 25, 18 and 29% [Geber et al., unpublished] | Yeast | -25 | -18 | -29 |