|GCN4 Deletion ||Deletion of GCN4 increases the replicative lifespan by 10% in the alpha strain .
GCN4 deletion decreases the lifespan in the alpha and a strain .
The chronological lifespan of GCN4 deletion is strongly decreased in the a strain . ||Yeast ||+10 ||— ||— |
|concA treatment ||The specific V-ATPase inhibitor concanatmycin A (concA) blocks VMA1 or VPH2 overexpression mutations ability to produce normal, tubular mitochondria. Treatment of young cells causes vacuolar acidity and loss of mitochondrial depolarization. Loss of ΔΨ is followed by mitochondrial fragmentation and aggregation that resembles mitochondrial phenotypes present in aged cells . ||Yeast ||— ||— ||— |
|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 .
||Yeast ||+23.1 ||+25.0 ||+34.0 |
|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 
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 .
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 .
Lifespan extension by DR is prevented in a strain lacking V-ATPase activity . ||Yeast ||+45.2 to +51.7 ||+42.9 to +50.0 ||+50.0 to +52.0 |
|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 . ||Yeast ||+27.8 ||+27.6 ||+21.6 |
|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 . ||Yeast ||-20.6 ||-22.4 ||-11.8 |
|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 . VMA2 deletion mutation decreases the mean replicative lifespan by 80% in the alpha strain . 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 . ||Yeast ||-80 to -83.9 ||-84.1 ||-70.0 |
|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 . ||Yeast ||+39.3 to +44.8 ||+39.3 to +48.3 ||+50.0 to +60.0 |
|HAC1 deletion ||Deletion of HAC1 decreases mean, median and maximum replicative lifespan by 10, 8 and 5%, respectively . ||Yeast ||+10.3 ||+8.3 ||+5.3 |
|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 . ||Yeast ||— ||— ||— |
|OSH2 deletion ||Deletion of OSH2 decreases mean chronological lifespan . ||Yeast ||— ||— ||— |
|AVO2 deletion ||Deletion of AVO2 extends chronological lifespan . ||Yeast ||— ||— ||— |
|AFG3 deletion ||Deletion of the mitochondrial AAA protease AFG3 increases replicative lifespan by 20% in the alpha and a strains , but decreases chronological lifespan by 37 - 51% in diploid cells .
AFG3 deletion changes mean, median and maximum lifespan by 15 to 26% 17 to 30% and -25 to +58%, respectively.
AFG3 deletion leads to reduced cytoplasmic mRNA translation and its lifespan extension is independent of Sir2 and Hac1, but requires Gcn4. AFG3 deletion further extends the lifespan of cell deficient in both SIR2 and FOB1, but fails to extend the lifespan of dietary restricted cells or cells lacking GCN4. Gcn4 protein levels are increased in afg3 mutants. The deletion of AFG3 fails to extend the replicative lifespan in the W303AR strain. AFG3 deletion does deletion extend the replicative lifespan at 15°C. ||Yeast ||-51 to +20 ||— ||— |
|YOL092W deletion ||Deletion of YOL092W decreases mean and maximum replicative lifespan by 36 and 21%, respectively. Lifespan of YOL092Y deletion mutants is extended by 0.5% glucose restriction . ||Yeast ||-36 ||— ||-21 |
|OSH6 deletion ||OSH6 deletion does not affect lifespan under normal conditions, but it abrogates the lifespan extension by 0.5% glucose restriction [Xia et al. unpublished]. ||Yeast ||— ||— ||— |
|OSH4 deletion ||Deletion of OSH4 decreases mean replicative lifespan by 18% [Xia et al., unpublished]. ||Yeast ||— ||— ||— |
|VAC14 deletion ||VAC14 mutants have a single vacuole and shortened lifespan on normal media . ||Yeast ||— ||— ||— |
|ZDS1 deletion ||Deletion of ZDS1 increases replicative lifespan by 37% in a SIR3-dependent manner .
Null mutation in ZDS1 causes 100-fold decrease in telomeric silencing, a nine-fold increase in rDNA silencing, reduces rDNA recombination, and decreases Sir3 phosphorylation . ||Yeast ||+37 ||— ||— |
|SKN1 deletion ||Chronological lifespan increased by 60% for single skn1 and double ipt1-skn1 deletion . ||Yeast ||+60 ||— ||— |
|TOS8 ||Deletion of TOS8 increases replicative lifespan increased by 35% in the alpha strain . ||Yeast ||+35 ||— ||— |
|WSC4 deletion ||Deletion of WSC4 decreases replicative lifespan by 30% in the alpha strain . ||Yeast ||-30 ||— ||— |
|YHF1 deletion ||Deletion of YFH1 decreases replicative lifespan by 50% . ||Yeast ||-50 ||— ||— |
|YHC3 deletion ||YHC3 deletion decreases 10-20% shortened lifespan . ||Yeast ||-10 to -20 ||— ||— |
|YIA6 deletion ||Deletion of YIA6 decreases replicative lifespan by 30% in the a strain . ||Yeast ||-30 ||— ||— |
|YOS9 deletion ||Deletion of YOS9 decreases replicative lifespan by 10% in the alpha strain . ||Yeast ||-10 ||— ||— |