| 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 |
| 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 |
| 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 |
| LAG1 deletion | A gene deletion of LAG1 in haploid cells results in a pronounced increase (approximately 50%) in mean and in maximum replicative lifespan in the YPHDF-1A strain [8195187], but has no significant effect on lifespan in stains W303R or PSY316 (N. Bishop, G.Liszt, and L. Guarente, unpublished]. The LAG1 transcribed is preferentially expressed in young cells. LAG1 null mutant is viable and has no obvious phenotypes but shows delayed ER to Golgi transport when combined with DGT1 mutation [10198056] and is synthetical lethal with LAC1 deletion. | Yeast | +50 | — | +50 |
| 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 |
| HXT17 deletion | HXT17 mutation extends both replicative and chronological lifespan as well as cancels out DR-induced replicative and chronological lifespan extension. Mean and maximum replicative lifespan are extended by 27 and 49%, respectively [21584246]. | Yeast | +27 | — | +49 |
| 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 |
| 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 |
| HXK2 deletion | Deletion of HXK2 extends mean and maximum replicative lifespan by about 53% and 33%, respectively. Limiting glucose availability by mutating HXK2 significantly extends replicative lifespan and provides a genetically model of DR [11000115]. HXK2 deletion increases oxygene consumption. Changes in gene expression HXK2 mutation are quite similar to those of dietary-restricted cells. In fact, HXK2 mutants have a transcriptional profile that significantly resembles DR cells and cell overexpressing HAP4 [12124627]. | Yeast | +53 | — | +33 |
| GUP1 deletion | GUP1 deletion extends mean and maximum replicative lifespan by 32 and 30%, respectively, as well as chronological lifespan. DR-induced maximal replicative lifespan extension is not further increased by GUP1 deletion, while gup1 mutant displayed longer chronological lifespan under DR [21584246]. | Yeast | +32 | — | +30 |
| 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 |
| RAS1 deletion | Deletion in RAS1 increases mean (23%) and maximum (29%) replicative lifespan (in SP1) [8034612]. RAS1 deletion increases replicative lifespan by 15% in the alpha strain [19030232]. However, deletion of RAS1 slightly shortens chronological lifespan (in SP1) [12586694]. | Yeast | +15 to +23 | — | +29 |
| FIS1 deletion | Deletion of FIS1 prolongs significantly mean and maximum lifespan by 13 and 29% as well as improves the fitness of old mother cells (in BY4741) [17173038]. | Yeast | +13 | — | +29 |
| GPA2 deletion | Deletion of GPA2 increases mean and maximum replicative lifespan by 40% and 26%, respectively. GPA2 deletion extends replicative lifespan by reducing cAMP-PKA activity and provides a genetic model for DR [11000115]. | Yeast | +40 | — | +26 |
| GPR1 deletion | Deletion of GRP1 increases mean and maximum replicative lifespan by 41% and 26%, respectively. GRP1 deletion mutants have also longer chronological lifespan. Deletion of GPR1 extends replicative lifespan by reducing cAMP-PKA activity and provides a genetically model for DR [11000115]. | Yeast | +41 | — | +26 |
| 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 |
| 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 |
| IMD2 deletion | Deletion of IMD2 did non-significantly decrease mean replicative lifespan by 1% and non-significantly increased maximum replicative lifespan by 21% [20550517]. | Yeast | -1 | — | +21 |
| IPK1 deletion | Deletion of IPK1 increases mean replicative lifespan by 41 - 40% in the alpha strain [16293764; 19030232]. IPK1 deletion extends mean and maximum replicative lifespan by 24 and 19%, respectively, and was non-synergistic with moderate DR [21584246]. | Yeast | +24 to +40 | — | +19 |
| 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 |
| CDC25 mutation | The CDC25-10 allele extends mean and maximum replicative lifespan by 34% and 18%, respectively, at 30 degree Celsius. cdc25-10 mutants have an extended replicative lifespan under AL. Growth on 0.5% glucose restriction does not further extend replicative lifespan of cdc25-10 mutants. CDC25 null mutant is not viable. CDC25 appears to act in the same genetic pathway as SIR2 and NPT1 and is suggested to be genetic model of DR [11000115]. | Yeast | +34 | — | +18 |
| 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 |
| Methionine restriction | Restriction of the methionine content in the culture extends mean and maximum lifespan by up to 29 and 16% (1/10 methionine content) [15141092]. | Yeast | +29 | — | +16 |
| Rapamycin treatment | Treatment with rapamcyin increases mean and maximum replicative lifespan by 19 and 16% Rapamycin fails to extend the lifespan of sir2 mutants or NAM treated wild-type cells [20947565]. Rapamcyin treatment increases mean chronological lifespan by by approximately by 80% in BY4742 [22790951].
Rapamycin extends chronological lifespan proportional with increasing concentrations from 100 pg/mL to 1 ng/mL [16418483] | Yeast | +19 to +50 | — | +16 |
| SML1 deletion | Deletion of SML1 increases non-significantly mean replicative lifespan by 3% and non-significantly maximum lifespan by 16% [20550517]. | Yeast | +3 | — | +16 |
GenAge
GenDR
