| 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 | — | — |
| 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 | — | — |
| PNC1 deletion | Deletion of PNC1 shortens replicative lifespan approximately by 10% [12736687] and largely prevents replicative lifespan extension of 0.5% glucose restriction. 0.5% glucose restriction slightly extends median replicative lifespan (by 10 - 15%) but not maximum replicative lifespan in pnc1Delta [14724176]. PNC1 deletion decreases chronological lifespan [17110466]. | Yeast | -10 | — | — |
| POL1 deletion | Mutation of POL1 results in a 20-60% reduction in mean lifespan (in SS111) [12024027] | Yeast | -20 to -60 | — | — |
| HST1 deletion | Deletion of HST1 blocks the residual replicative lifespan extension by hxk2 mutant in a sir2;fob1;hst2 triple mutant background [16051752]. However, DR can increases the replicative lifespan to a similar extent in sir2;fob1;hst1;hst2 quadruple mutant cells as in sir2;fob1 double mutant cells under 0.5, 0.05 and 0.005% glucose conditions and even by hxk2 deletion mutant [16741098; 17129213]. | Yeast | — | — | — |
| PUF4 deletion | Deletion of PUF4 has no effect on replicative lifespan in either uth4-14c (C-terminal truncation) or UTH4 background. However, PUF4 is required for lifespan extension by the semi-dominant Sir4-42 allele in the uth4-14c background [9150138].
PUF4 is required for nucleolar relocalization of Sir3 in a Sir4-42 background [9150138]. puf4;mpt5 double deletion strain has increased telomere silencing reltive to the mpt5 single mutant [9651685]. | Yeast | — | — | — |
| PCK1 deletion | Loss of Pck1 activity blocks chronological lifespan extension caused by water starvation. Knockout of PCK1 dramatically reduces chronological lifespan in both water (extreme DR) and glucose-containing medium. Deletion of SIR2 does not alter the lifespan of PCK1 deletion mutant, pck1-K514R, and pck1-K514Q mutants [19303850]. | Yeast | — | — | — |
| BNA6 deletion | Deletion of BNA6 (alias QPT1) has no effect on replicative lifespan and is not required for lifespan extension by DR, but is lethal with mutation of NPT1 [11000115]. Deletion of BNA6 decreases chronological lifespan [17110466]. | Yeast | — | — | — |
| PCK1 mutation | pck-1-K514Q mutation which abrogates enzymatic activity of Pck1, just like SIR2 deletion, extends chronological lifespan in water. Deletion of SIR2 does not alter the lifespan of PCK1 deletion mutant, pck1-K514R, and pck1-K514Q mutants [19303850]. | Yeast | — | — | — |
| ESA1 mutation | esa1-531 mutant has an even shorter chronological lifespan than PKA1 deletion mutant in both 2% glucose (ad libitum) and water (extreme DR) at 30 degree Celsius, a semipermissive temperature. At the permissive temperature (25 degree Celsius) there is little difference [19303850]. | Yeast | — | — | — |
| RAD1 mutation | Deletion of RAD1 has no effect on replicative lifespan [10207108]. | Yeast | — | — | — |
| GSH1 deletion | Deletion of GSH1 confers deficiency in glutathione biosynthesis and further increases chronological lifespan under 0.5% glucose restriction, but does not extend chronological lifespan under 2% glucose [18840459]. Therefore, GSH1 has a positive interaction with DR [18840459]. | Yeast | — | — | — |
| SCH9 Deletion | SCH9 deletion increases chronological lifespan by up to threefold. Stress-resistance transcription factors Msn2/Msn4 and protein kinase Rim15 are required for this life-extension. Deletion of the mitochondrial antioxidant enzyme superoxide dismutase gene SOD2 prevents the increased chronological lifespan caused by SCH9 deletion [11292860]. Mutations that decrease the activity of the Ras/Cyr1/PKA pathway also extend longevity and increase stress resistance by activating transcription factors Msn2/Msn4 and Sod2 [12855292]. SCH9 deletion mutants exhibit more than 3-fold extension of chronological lifespan. By day 9 of medium depletion all the wild-type cells were dead while 50% sch9 mutants survived [17710147]. Deletion of SCH9 also increases resistance to heat shock and oxidative stress [11292860], and increases replicative lifespan by 18% (in DBY746) [12586694]. SCH9 deletion increases the replicative lifespan by 40% in the alpha strain [18340043] and increases mean chronological lifespan by 97 - 246% (97, 133, 154, 226, 246) in diploid cells [21447998]. Mutation or deletion of SCH9 increases resistance to oxidants and extends chronological lifespan [11292860; 16286010]. The extended lifespan of SCH9 deletion mutants is not further extended by low glucose DR and is independent of Sir2 [16293764]. Deletion of RIM15 or GIS1 reverses chronological lifespan extension associated with sch9Delta. Water restriction further increases chronological lifespan of sch9Delta [18225956]. Deletion of SCH9 results in a longer chronological lifespan [21076178]. | Yeast | +18 to +300 | — | — |
| ERG3 deletion | Deletion of ERG3 decreases replicative lifespan under AL, cancels out replicative lifespan extension of 0.5% glucose DR and results under DR also into a shorter replicative lifespan than under AL [18690010]. | Yeast | — | — | — |
| RAD27 deletion | Deletion of RAD27 results in signs of premature aging and approximately 60% reduction in mean replicative lifespan [12024027]. | Yeast | -60 | — | — |
| SUR4 deletion | Deletion of SUR4 cancels out replicative lifespan extension of 0.5% glucose DR [18690010]. | Yeast | — | — | — |
| RAS2 deletion | RAS2 deletion causes a 23% decrease in mean and a 30% decrease in maximum lifespan [8034612]. Deletion of RAS2 leads to a longer chronological lifespan [21076178]. Deletion of the RAS2 gene, which functions upstream of CYR1, doubles the mean chronological lifespan by a mechanism that requires Msn2/4 and Sod2 [12586694]. DR further extends chronological lifespan of ras2Delta [18225956]. | Yeast | -23 | — | -30 |
| LCB4 deletion | Deletion of LCB4 increases replicative lifespan and cancels out replicative lifespan extension of 0.5% glucose DR [18690010]. | Yeast | — | — | — |
| RAD52 deletion | Deletion in RAD52 causes a 75% reduction in mean replicative lifespan in PSY316 strain [10207108]. Similiar reduction of lifespan occurs in strains W3031-A and W303R [M. Baeberlein, M. McVey, and L. Guarente, unpublished].
RAD51 is required for formation of extrachromosomal rDNA circles [10207108], but not for replication fork pasuing nor DNA breakage with the rDNA [10693764]. | Yeast | -75 | — | — |
| RAD7 deletion | Deletion of RAD7 has no effect on replicative lifespan in PSY316 [10207108].
Mutation in RAD7 results in decrease repair of the non-transcribed strand in rDNA [8604332]. | Yeast | — | — | — |
| NFU1 deletion | NFU1 mutation slightly shortens the chronological lifespan under AL and the chronological lifespan of NFU1 mutants is not extended by 0.5% glucose DR [20421943]. | Yeast | — | — | — |
| RAD9 deletion | Deletion results in mutants with a 2-fold decrease in mean and maximum chronological lifespan under conditions of nutrient depletion [17710147]. Mutation of RAD9 shortens lifespan by 30% in DBY747 [7806576] and in strain W303 [11290710].
RAD9 mutation has no effect on telomeric silencing or length [10924458]. | Yeast | -30 | — | — |
| FET3 deletion | FET3 mutation slightly shortens chronological lifespan under AL. Its chronological lifespan is not extended by 0.5% glucose or amino-acid DR [20421943]. FET3 is one of several iron related genes that are up-regulated in response to increasing strength of glucose DR [18679056]. | Yeast | — | — | — |
| PDE2 Deletion | Deletion of PDE2 decreases mean replicative lifespan by 26% [11000115] and also results in a shorter chronological lifespan [21076178].
PDE2 null mutant are sensitive to oxidative stress [10394911]. | Yeast | -26 | — | — |
| 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 |
GenAge
GenDR
