| 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 It also extends the lifespan of NYV1 mutant [Geber et al., unpublished].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 |
| OSH7 overexpression | Overexpression of OSH7 extends mean replicative lifespan. PERG6-OSH7 does not extend the maximum lifespan significantly [Xia et al., unpublished]. | Yeast | — | — | — |
| Overexpression of truncated TLC1 | Overexpression of a truncated allele of TLC1 abrogates telomere silencing [7545955], shortened telomeres and extends replicative lifespan approximately by 20% [9275199]. Deletion of TLC1 might decrease replicative lifespan [Nugent et al., 1996]. | Yeast | +20 | — | — |
| 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 | — | — | — |
| PNC1 overexpression | Cells with 5 copies of PNC1 have a 70% longer replicative lifespan which is cancelled out by SIR2 deletion. Overexpression of PNC1 suppresses the effect of exogenously added nicotinamide on Sir2-dependent silencing at HM loci, telomeres and rDNA loci [12736687; 14729974]. PNC1 overexpression suppresses the inhibitory effect of exogenously added NAM on silencing, lifespan, and Hst1-mediated transcriptional repression [14729974]. Increased expression of PNC1 is both necessary and sufficient for replicative lifespan extension by DR and low-intensity stress. Under non-stressing conditions (2% glucose, 30 degree Celsius), a strain with additional copies of PNC1 (5XPNC1) has 70% longer replicative lifespan than the wild-type and some cells live for more than 70 divisions. Neither DR nor heat stress further increase the lifespan of the 5XPNC1 strain [12736687]. | Yeast | +70 | — | — |
| RAS1 overxpression | No lifespan extension results from overexpression of RAS1 (in SP1) [8034612]. | Yeast | — | — | — |
| 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 |
| SCP1 overexpression | Overexpression of SCP1 leads to elevuated ROS levels and reduces chronological lifespan [15024029]. | Yeast | — | — | — |
| SGS1 overexpression | Overexpression of SGS1 extends the maximum lifespan of cells lacking SRS2, but not the mean lifespan [11861900]. | Yeast | — | — | — |
| SIR2 overexpression | Integration of a second copy of SIR2 into the wild-type strain leads to an extension of replicative lifespan by around 35% in W303R strain[10521401]. 0.05% glucose restriction further extends replicative lifespan of SIR2 overexpression mutant [15328540]. Overexpression extends replicative lifespan in several strains, but not in PSY316 | Yeast | +35 | — | — |
| SNF1 overexpression | Overexpression (high-copy 2 micro expression) of SNF1 shortens replicative lifespan to 75% of wild-type and is accompanied by signs of premature ageing, including proegressive sterility, enlargment and fragmentation of the nucleus, redistribution of Sir3 to the nucleus, and more rapid accumulation of extrachromosomal rDNA circles [10921902]. SNF1 overexpression also reduced chronological lifespan [19164565]. | Yeast | -25 | — | — |
| SOD1 overexpression | The overexpression of Sods, mitochondrial Sod2 and cytosolic CuZnSod (Sod1), in combination delays the age-dependent reversible inactivation of mitochondrial aconitase, a superoxide-sensitive enzyme, and extends chronological lifespan by 30% [12586694]. Overexpression of SOD1 with CCS1 levuates the level of Cn, Zn-Sod activity and increased chronological lifespan. However overexpression of SOD1 without high cooper or simultonous overexpression of CCS1 shortened both chronological and replicative lifespan [15659212]. Overexpression of SOD1 has no effect on replicative lifespan [10224252].
| Yeast | — | — | — |
| SOD2 overexpression | Combined overexpression of SOD1 and SOD2 extends chronological lifespan by 30% in EG103 strain [12586694].
| 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 [15126388]. SSD1-V also dramatically increases chronological lifespan with lifespan twice as long as ssd1-d cells [19570907].
Addition of SSD1-V allele to an ssd1-d strain suppresses the short lifespan of an MPT5 deletion mutant [11805047] 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 [11805047]. SSD1-V also suppresses the synthetic lethality caused by deletion of MPT5 in combination with a mutation in SWI4, SWI6, or CCR4 [11805047]. SSD1-V suppresses mutations that affect cell wall stability [1545797; 8386319], RNA polymerase III activity [8510644], RNA splicing [10446233], and PKA activity [1848673; 8200529]. | Yeast | +50 to +100 | — | — |
| 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 |
| 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 |
| YDC1 overexpression | YDC1 overexpression decreases chronological lifespan by 40% [19059240]. | Yeast | -40 | — | — |
GenAge
GenDR
