| SWI4 deletion | Deletion of SWI4 shortens replicative lifespan by approximately 90% [11805047]. SSD1-V partially suppresses the short lifespan of a swi4 mutant.
Mutation of swi4 results in slow growth and temperature sensitivity, both of which are suppressed by SSD1-V [11805047]. | Yeast | -90 | — | — |
| 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 |
| 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 | — | — |
| 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 |
| CCR4 deletion | Deletion of CCR4 increases mean chronological lifespan by 20 - 41% (20, 33, 41) in diploid cells [21447998]. In W303R CCR4 deletion shortens replicative lifespan by approximately 80% and results in temperature sensitivity that is suppressed by SSD1-V. SSD1-V partially suppresses the short-lifespan of ccr4 mutant. CCR4 mutation is synthetically lethal in combination with deletion of MPT5 in the absence of SSD1-V [11805047]. | Yeast | -80 to +20 | — | — |
| SIP1 deletion | Deletion of SIP1 decreases replicative lifespan by 80%, without accompying aging biomarkers in S288C strain [10921902]. | Yeast | -80 | — | — |
| 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 | — | — |
| TPS1 deletion | Deletion of TPS1 decreases intracellular trehalose concentration and shortens the mean chronological lifespan by 74% (at 30 degree Celsus in BY4742) [22783207]. | Yeast | -74 | — | — |
| ATP1 deletion | Deletion of ATP1 increases chronological lifespan by up to 50% [17492370], but decreases replicative lifespan by 70% in the alpha strain [18340043]. | Yeast | -70 to +50 | — | — |
| Top3b knockout | Homozygous disruption of Top3b results in a normal development but a shorter lifespan (by approximately 70%) accompanied by lesions in multiple organs in C57BL/6 [11331780]. | Mouse | -70 | — | — |
| INM2 deletion | Deletion of INM2 decreases replicative lifespan by 70% in the alpha strain [19030232]. | Yeast | -70 | — | — |
| RAD50 deletion | RAD50 mutations result in a 70% reduced replicative lifespan [10207108]. | Yeast | -70 | — | — |
| Drd4 knockout | Drd4 knockout mice, when compared with wild-type and heterozygous mice, display a 7 - 9.7% decrease in lifespan, reduced spontaneous locomotor activity, and no lifespan increase when reared in an enriched environment [23283341]. | Mouse | -7 to -9.7 | — | — |
| TPS2 deletion | Deletion of TPS2 has no effect on replicative lifespan and does not prevent lifespan extension by high osmolarity [12391171]. Deletion of TPS2 decreases intracellular trehalose concentration and shortens mean chronological lifespan by 61% (at 30 degree Celsus in BY4742) [22783207].
TPS2 is required for trehalose biosynthesis in response to osmotic stress [8444170]. | Yeast | -61 | — | — |
| SIP2 deletion | Deletion of the N-myristoylprotein SIP2 results in reduced resistance to nutrient deprivation and a 60% shorter lifespan accompanied by signs of accelerated aging such as loss of silencing from telomeres and mating loci, redistribution of Sir3 to the nucleolus, progressive sterility, nucleolar fragmentation and enlargement, and accumulation of extrachromosomal rDNA [10921902].
SIP2 deletion increases replicative lifespan by 20% in the alpha strain [19030232].
SIP1 null mutation causes increase in the intracellular ATP and NAD+ levels in both young cells (generation 0-1) and older cells (generation 4), but the increase is greater in older cells [10921902]. | — | -60 to +20 | — | — |
| RAD27 deletion | Deletion of RAD27 results in signs of premature aging and approximately 60% reduction in mean replicative lifespan [12024027]. | Yeast | -60 | — | — |
| YGR071C deletion | Deletion of YGR071C decreases replicative lifespan by 60% in the alpha strain [19030232]. | Yeast | -60 | — | — |
| CLA4 deletion | Deletion of CLA4 decreases replicative lifespan by 60% in the alpha strain [18340043; 19030232]. | Yeast | -60 | — | — |
| SGS1 mutation | Deletion of SGS1 causes premature aging including a shortened replicative lifespan by approximately 60%, sterility, fragmentation of the nucleolus and redistribution of the Sir3 silencing protein from telomeres to the nucleolus [Sinclair et al, 1997]. Mutation in SGS1 shortens replicative lifespan by 30% [11290710]. Introduction of mutant allele with a point mutation (SGS1 K(706)-->A) in the RecQ helicase domain that eliminates the DNA helicase activity of Sgs1 fails to rescue the premature aging of the sgs1Delta strain, demonstrating that Sgs1 DNA helicase activity is required for a normal lifespan [11861900].
Most cell death in sgs1 mutant cells is caused by a stochastic cell cycle arrest that is associated with a large-budded terminal morpholgy [McVey et al, 2001]. Overexpression of SIR2 or deletion of FOB1 extend lifespan of only those sgs1 cells that escape this arrest [11290710; 10230397].
sgs mutants have greater rate of telomere loss than wild-type cells in the abscence of telomerase [11179234]. | Yeast | -60 | — | — |
| VAM3 deletion | Deletion of VAM3 decreases mean replicative lifespan by 56% both on AL [19030232] and on moderate DR [18690010] (in BY4742/alpha strain). | Yeast | -56 | — | — |
| AFG3 deletion | Deletion of the mitochondrial AAA protease AFG3 increases replicative lifespan by 20% in the alpha and a strains [18340043], but decreases chronological lifespan by 37 - 51% in diploid cells [21447998].
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 | — | — |
| 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 | — | — |
| 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 |
| RRG1 deletion | Deletion of RRG1 decreases replicative lifespan by 50% in the alpha strain [19030232]. | Yeast | -50 | — | — |
| GMC2 deletion | Deletion of GMC2 decreases replicative lifespan by 50% in the alpha strain [19030232]. | Yeast | -50 | — | — |
GenAge
GenDR
