| 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HES1 levels by an ERG6 promoter reduces mean, median and maximum replicative lifespan by 25, 18 and 29% [Geber et al., unpublished] | Yeast | -25 | -18 | -29 |
| 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 It also extends the lifespan of NYV1 mutant [Geber et al., unpublished].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 |
| 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 |
| 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 | — |
| CIT2 overexpression | Overexpression of CIT2 has no effect on replicative lifespan [10224252]. | Yeast | — | — | — |
| HSP104 overexpression | Overexpression of HSP104 driven by GAL promoter is insufficient to extend replicative lifespan [9851879]. Overproduction of HSP104 in wild-type cells has no effect on replicative life span, but suppresses the reduced lifespan of Sir2-deficient cells [17908928]. HSP104 overproduction is sufficient to induce thermotolerance [8643570]. | Yeast | — | — | — |
| LAG2 overexpression | When LAG2 is overexpressed in SP1 strain, the mean and maximum replicative lifespan is extended by about 36% and 54%, respectively. Overexpression induced at generation 12 similarly increases replicative lifespan [8760941]. | Yeast | +36 | — | +54 |
| MPT5 overexpression | Overexpression of MPT5 from the ADH promoter extends replicative lifespan by about 20% in W303R [11805047] and by 25% in PSY142 [9150138].
MPT5 overexpression suppresses the temperature phenotype of POP2 mutant [9504907]. | Yeast | +20 to +25 | — | — |
| 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 | — | — | — |
| RPL31A deletion | Deletion of RPL31A increases mean replicative lifespan by 45% [16293764]. Mean replicative lifespan increases by 35% in the alpha strain and 50% in a strain [19030232; 18423200]. Mean replicative lifespan of the RPL31A deletion mutant increases by 35% in the ORF collection and by 29% in the remade strain [22377630]. RPL31A deletion increases significantly replicative lifespan [17174052]. Deletion of RPL31A extends replicative lifespan and is not further extended by 0.05% glucose restriction [18423200]. | Yeast | +29 to +50 | — | — |
| 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 | — | — |
| SIR3 activating mutation | The S755A allele of SIR3 (which prevents phosphorylation of Sir3) results in a 40% increase in mean and maximum lifespan [12640455]. | Yeast | +40 | — | +40 |
| 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 | — | — |
| 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 | — | — | — |
| Elevation of histone expression | The elevation of histone expression promotes replicative lifespan extension [20832724]. | Yeast | — | — | — |
| 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 | — | — | — |
GenAge
GenDR
