| VMA2 deletion | VMA2 deletion mutants have a reduced ΔΨ and mitochondrial morphology similar to aged cells. The restoration of the vacuolar acidity in daughter cells requires V-ATPase activity as it is eliminated in VMA2 deletion mutant cells [23172144]. VMA2 deletion mutation decreases the mean replicative lifespan by 80% in the alpha strain [18340043]. Deletion of VMA2 decreases mean, median and maximum replicative lifespan by 84%, 84% and 70%, respectively. DR (0.5% glucose restriction) does not extend the replicative lifespan of VMA2 and shortens it even more [23172144]. | Yeast | -80 to -83.9 | -84.1 | -70.0 |
| KSS1 deletion | Deletion of KSS1 results in increased sensitivity to heat shock and oxidative stress and a 25% reduction in median chronological lifespan [17662940]. | Yeast | — | -25 | — |
| AVT1 deletion | Deletion of AVT1 accelerates the development of age-induced mitochondrial dysfunction without effecting the kinetics of vacuolar acidity decline and prevents the suppression of mitochondrial dysfunction by VMA1 and VPH2 overexpression without affecting vacuolar acidity. AVT1 deletion decreases mean, median and maximum lifespan by 21, 22, and 12%, respectively [23172144]. | Yeast | -20.6 | -22.4 | -11.8 |
| 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HES1 levels by an ERG6 promoter reduces mean, median and maximum replicative lifespan by 25, 18 and 29% [Geber et al., unpublished] | Yeast | -25 | -18 | -29 |
| HAC1 deletion | Deletion of HAC1 decreases mean, median and maximum replicative lifespan by 10, 8 and 5%, respectively [23167605]. | Yeast | +10.3 | +8.3 | +5.3 |
| 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 It also extends the lifespan of NYV1 mutant [Geber et al., unpublished].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 |
| RPS6B deletion | RPS6B deletion increases mean replicative lifespan by about 30% [16293764]. Deletion of RPS6B, but not of the RPS6A paralog increases replicative median lifespan robustly by 45% [17174052]. | Yeast | +30 | +45 | — |
| Moderate DR | Moderate DR is the restriction of glucose concentration from 2% (*ad libitum*) to 0.5%, which extends the mean, median and maximum replicative lifespan by 45 - 52%, 43 - 50% and 50 - 52%, respectively [23172144]
Moderate DR increases vacuolar acidity in young cells and prevents the decline of vacuolar acidity in aging cells. DR also suppresses mitochondrial dysfunciton of aged cells (21 divisions) in a V-ATPase-dependent manner [23172144].
Constitutively activating PKA signaling by deleting the Ras GTPase-activating protein IRA2 reduces vacuolar acidity and accelerates the development of mitochondrial dysfunction in aging cells and prevents DR-mediated enhancement of vacuolar acidity and suppression of mitochondrial dysfunction [23172144].
Lifespan extension by DR is prevented in a strain lacking V-ATPase activity [23172144]. | Yeast | +45.2 to +51.7 | +42.9 to +50.0 | +50.0 to +52.0 |
| 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 |
| CYR1 mutation | The CDC35-1 allele of the adenylate cyclase CYR1 confers a 75% extension of replicative lifespan at 25 degree Celsius [11000115]. cyr1-1 mutation extends median chronological lifespan by 28-47% and is non-addative with lifespan extension conferred by overxpression of human MAPK1 [17662940]. | Yeast | +75 | +28 to 47 | — |
| AVT1 overexpression | Overexpression of AVT1 prevents mitochondrial dysfunction, prevents alterations in mitochondrial structure and ΔΨ of aged cells even through the vacuolar acidity is reduced in these cells. AVT1 overexpression extends the mean, median and maximum replicative lifespan by 28, 28, and 22%, respectively [23172144]. | Yeast | +27.8 | +27.6 | +21.6 |
| HSP12 deletion | HSP12 deletion slightly increases mean, medium, and maximum replicative lifespan by 24, 27, and 3% under AL, but totally abolishes the lifespan extending effect of moderate DR [Alan Morgan, personal communication; Herbert et al. in press].
HSP12 deletion has no effect on resistance to variety of stresses (including oxidative stress) [Alan Morgan, personal communication]. | Yeast | +24 | +27 | +3 |
| 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 | — |
| RPL10 deletion | Heterozygosity for RPL10 deletion increases median replicative lifespan by 24% [17174052]. | Yeast | — | +24 | — |
| IDH2 deletion | Deletion of IDH2 increases the mean replicative lifespan by about 30% [16293764]. IDH2 deletion extends mean replicative lifespan by 20% in the alpha strain and in a strain [19030232; 18340043]. IDH2 deletion extends mean, median and maximum lifespan by 15, 19 and 15% [23167605]. | Yeast | +15.4 to +30 | +19.2 | +15.4 |
| TOR1 Deletion | TOR1 deletion extends mean and maximum replicative lifespan by 21 and 25% [16293764] as well as chronological lifespan [21076178]. This lifespan extension is independent of SIR2 and additive with deletion of FOB1 [16293764]. Deletion of TOR1 fails to increase the replicative lifespan of a sir2 mutant [20947565]. Deletion of TOR1 substantially extends chronological lifespan, increasing median survival almost 3-fold (wild-type 4.5 days, tor1 null 12 days), i.e. by 167%. By 21 days in culture, the vast majority of wild-type cells had died (>99.9%), whereas many tor1 null cells remained viable. Deletion of TOR1 also extends the chronological lifespan of the relatively short-lived BY4742 strain, one of the two haploid genetic backgrounds of the widely used Yeast Knockout Collection available from Open Biosystems. Deletion of TOR1 fails to extend chronological lifespan in Petite strains that are unable to respire [17403371]. TOR1 deletion increases replicative lifespan by 30% in the alpha strain and 20% in a strain [19030232]. TOR1 deletion mutant have and increased mean and maximum replicative lifespan by 21% and 6%, respectively [21931558]. Deletion of TOR1 extends replicative lifespan as well as chronological lifespan [21076178] and glucose restriction fails to further extend the long replicative lifespan of tor1Delta [16293764; 16418483; 18225956]. Water starvation (extreme DR) further extends chronological lifespan of tor1 mutants [18225956]. | Yeast | +21 to +30 | +167 | +6 to +25 |
| TMA19 deletion | Deletion of TMA19 increases median replicative lifespan by 16% (P<0.02) [16806052]. TMA19 deletion increases mean replicative lifespan by 25-30% in the alpha and a strains [19030232]. | Yeast | +25 to +30 | +16 | — |
| Petite | Respiratory deficient petite cells in YPK9 strain have a replicative lifespan that is extended by 39%. This lifespan extension is strain-specific as Petite cells in W303 have lifespan identical to grande cells and petite cels in strains SP1-1 and A364A have a shorter lifespan than grande cells [10224252].
Respiratory defective petite cells display defective mitochondria and are unable to grow on glycerol. | Yeast | +39 | — | — |
| Diazaborine | Treatment of wild-type cells with 15 microgram/ml diazaborine extends mean (24.7 -> 36.9) and maximum replicative lifespan [18423200]. | Yeast | — | — | — |
| PHB1 deletion | Deletion of PHB1 results in a slight reduction in mean and maximum replicative lifespan and a defect in mitochondrial membrane potential. When both PHB1 and PHB2 genes are deleted, the mean replicative lifespan is reduced by one third (30%) that of the wild-type strain [9259555]. Deletion of PHB1 decreases replicative lifespan by 20% [12882345]. Phenotypic changes characteristic of aging cells (e.g. lengthening of cell cycle and specific morphological changes) suggests that PHB1;PHB2 double mutants undergo premature aging, not simply reduction of viability [9259555].
There is no reduction in stress resistance or bulk growth rate in PHB1 mutants. PHB1;PHB2 double mutant have a strong defect in mitochondrial potential, while PHB1 mutant have only a slight defect [9259555]. PHB1 deletion is synthetical lethal with mutation of outer mitochondrial membrane proteins, Mdm12, Mdm10, or Mmm1 [9632789]. | Yeast | -30 | — | — |
| Deletion of mitochondrial DNA | Activation of the retrograde response by deletion of mitchondrial DNA (rho0) extends mean and maximum replicative lifespan by 24 - 51% and 15 - 65%, respectively [10224252]. Lifespan extension associated with impaired mitochondria depends on a retrograde intracellular signalling involving at leas three transcription factors, which adjust nuclear gene expression an induce shift of metabolism from Krebs cycle to the glyoxylate cycle [Refs 41,42 i Lee et al., 2002]. | Yeast | +24 to +51 | — | +15 to +65 |
| PHB2 deletion | PHB2 deletion leads to a slight reduction in both mean and maximum replicative lifespan, and when both PHB1 and PHB2 genes are deleted, the mean replicative lifespan is reduced by 40% [9259555]. Deletion of PHB2 decreases replicative lifespan by 30% [12882345]. Phenotypic changes characteristic of aging cells (e.g. lengthening of cell cycle and specific morphological changes) suggests that PHB1;PHB2 double mutants undergo premature aging, not simply reduction of viability [9259555].
PHB2 mutants exhibit no reduction in stress resistance or bulk growth rate. PHB1;PHB2 double mutant have a strong defect in mitochondrial potential [9259555].
Prohibitin-dependent mutation pbd1 and pdb2 behave in a different manner and probaly affect different aspects of prohibitin function. pdb1 mutants slightly extended lifespan by 11%, whereas in contrast, the pdb2 mutation results in a shortening in both the mean- and the maximum-lifespan (by 28 and 17%, respectively). pdb1 mutation also reduces chronological lifespan. Reducing the expression of the PHB2 in the pbd mutants retards the rate of growth and affects replicative lifespan [16710639]. | Yeast | -30 | — | — |
| Gonadermasides D treatment | Application of gonadermasides D significantly increases the replicative lifespan in the K6001 strain by regulating UTH1 [21512225]. | Yeast | — | — | — |
| Ganodermasides A treatment | Application of Ganodermasides A extends the replicative lifespan in K6001 strain by regulating UTH1 expression [20093034]. | Yeast | — | — | — |
GenAge
GenDR
