| SRS2 deletion | Deletion of SRS2 shortens mean replicative lifespan by 50% [11290710]. Overexpression of SGS1 increases maximum, but not mean lifespan of SRS2 mutants [11861900]. Deletion of SRS2 is synthetical lethal in combination with deletion of SGS1 [11290710]. | Yeast | -50 | — | — |
| HSC82 deletion | Deletion of HSC82 has no effect on replicative lifespan, but shortens chronological lifespan [11361336]. | Yeast | — | — | — |
| HSP104 deletion | Deletion of HSP104 leads to a 14% [9851879] to 40% [17908928] reduction in mean replicative lifespan, therfore it is required for required for longevity. Exposure of cells to transient sub-lethal heat-stress extends mean lifespan by 12% while decreasing maximum lifespan by 14%. This effect does not occur in an HSP104 null mutant [9851879]. HSP104 null mutant is viable but displays reduced high temperature survival [8643570]. | Yeast | -14 to -40 | — | — |
| 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 | — | — | — |
| 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 |
| LAC1 deletion | Deletion of LAC1 the homolog of LAG1 [9872981] has no effect on replicative lifespan in strain W303R and PSY316 [N. Bishop, G. Liszt, and L. Guarente, unpublished]. LAC1 null mutant has no obvious growth defect [10198056], but is synthetically lethal with LAG1 mutation [9872981]. | Yeast | — | — | — |
| 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[8195187], but has no significant effect on lifespan in stains W303R or PSY316 (N. Bishop, G.Liszt, and L. Guarente, unpublished].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 |
| 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 |
| LAG2 deletion | Deletion of LAG2 in haploid SP1 strain does not affect growth, but results in a 50% decrease in the mean and maximum replicative lifespan [8760941]. | Yeast | -50 | — | -50 |
| Mating type heterozygosity | Mating type heterozygosity results in an approximately 20% mean replicative lifespan reduction, which occurs in both haploid and diploid cells (W303R) [10521401] and is likely due to increased homologous recombination [8454201] and rDNA circle formation [10521401]. | Yeast | -20 | — | — |
| MPT5 deletion | Deletion of MPT5 shortens replicative lifespan by about 50% [9150138; 7859289]. MPT5 deletion decreases average chronological lifespan by 50%, which is rescued to the wild-type level by PKC1 overexpression [17172436].
MPT5 mutants are temperature sensitive [7845352], hypersensitive to mating pheromone [9154842], and null mutants exhibit increased silencing at telomeres and decreased rDNA silencing [9584615]. Deletion of MPT5 is synthetical lethal with mutation of either SWI4, SWI6, or CCR4 in an ssd1-d background [11805047]. MPT5 is required for relocalization of the SIR complex to the nucleolus in sir4-42 strain [7859289]. | Yeast | -50 | — | — |
| 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 | — | — |
| MSN2 MSN4 double mutation | Deletion of MSN2 and MSN4 extends replicative lifespan and is further extended by cyr1::mTn [14741356]. Deletion of MSN2 and MSN4 does not significantly decrease chronological lifespan under AL, but attenuates chronological lifespan extension by water starvation and 0.5% glucose restriction [18225956] as well as cancels out lifespan extension of cyr1::mTn [14741356] and decreases chronological lifespan extension of ras2 deletion mutant [12586694]. Simulatnous deletion of MSN2 and MSN4 has no effect on chronological lifespan, but prevents lifespan extension by RAS2 deletion [12586694]. msn2 msn4 has no effect on replicative lifespan in PSY316, and does not prevent lifespan extension by DR [11000115] or by high osmolarity [12391171]. | Yeast | — | — | — |
| NCA3 deletion | Disruption in NCA3 shortens mean (87% of normal), nut not maximum replicative lifespan without causing any other gross changes in cell cycle parameters of growth characteristics [8810036].
In combination with an NCA2 disruption, NCA3 disruption causes a cryosensitive phenotype on non-fermentable carbon sources due to a defect in the F1-F0 ATP synthetase due to misbalancing of alternate spliceforms of mitochondrial mRNA encoding subunits 6 and 8 of the synthase [7586026]. | Yeast | -87 | — | — |
| DNM1 deletion | Deletion of DNM1 extends significantly mean and maximum lifespan by 49 and 111% in FY10 strain and by 15 and 12% in BY4741 strain [17173038]. | Yeast | +15 to +49 | — | +12 to +111 |
| 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 |
| NMT1 mutation | nmt1-451D allele shortens mean and maximum replicative lifespan by 47 and 44% at 24 degree Celsius (permessive temperature). Mutants have decreased resistance to acute and gradual nutrient deprivation, even at the permissive temperature [10921902]. A NMT null mutant is lethal. | Yeast | -47 | — | -44 |
| 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 |
| NNT1 deletion | Deletion of NNT1 decreases mean and maximum lifespan by 9 and 19%. 0.5% glucose DR extends the mean and maximum lifespan of NNT1 deletion mutants by 35 and 40%. NNT1 deletion decreases rDNA silencing [12736687]. | Yeast | -9 | — | -19 |
| 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 |
| NAM treatment | Treatment with NAM reduces mean and maximum replicative lifespan by 28 and 37%. NAM treatment blocks the lifespan extending effect of rapamycn [20947565]. | Yeast | -28 | — | -37 |
| NPT1 deletion | NPT1 deletion decreases replicative lifespan by 50% [17482543] as well as chronological lifespan [17110466]. Deletion of NPT1 shortens the lifespan in W303R. Replicative lifespan extension of cdc25-10 mutation (assumed to act as a genetic DR-mimetic) is cancelled out by NPT1 deletion [11000115].
NPT1 mutation results in loss of telomere and rDNA silencing [10841563], an effect that is likely caused by a loss of SIR2 activty due to decreased NAD levels. Mutation of NPT1 is synthetical lethal with mutation of QPT1 [11000115]. | Yeast | -50 | — | — |
| NPT1 overexpression | Increased dosage of NPT1 increases SIR2-dependent silencing, stabilizes the rDNA locus and extends replicative lifespan by up to 60%. 0.5% glucose restriction does not significantly further increase replicative lifespan of NPT1 overexpression [11884393]. NPT1 deletion decreases replicative lifespan by 50% [17482543] as well as chronological lifespan [17110466]. Deletion of NPT1 shortens the lifespan in W303R. Replicative lifespan extension of cdc25-10 mutation (assumed to act as a genetic DR-mimetic) is cancelled out by NPT1 deletion [11000115]. | Yeast | +60 | — | — |
| 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 | — | — |
| 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 | — | — |
GenAge
GenDR
