| MPT5 | — | Overexpression of MPT5 from the ADH promoter extends replicative lifespan by about 20% in W303R [11805047] and by 25% in PSY142 [9150138], whereas the deletion of MPT5 shortens 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 overexpression suppresses the temperature phenotype of POP2 mutant [9504907]. MPT5 is required for relocalization of the SIR complex to the nucleolus in sir4-42 strain [7859289]. | Budding yeast |
| NDE1 | NADH Dehydrogenase, External 1 | Overexpression of NDE1 and NDE2 increases intracellular NAD/NADH ratio by lowering NADH concentration and increases replicative lifespan by 20-25%. This lifespan extension is non-additive 0.5% glucose restriction [14724176]. Deletion of NDE1 extends chronological lifespan [16436509]. | Budding yeast |
| NDE2 | NADH Dehydrogenase, External 2 | Overexpression of NDE1 and NDE2 increases intracellular NAD/NADH ratio by lowering NADH concentration and increases replicative lifespan by 20-25%. This lifespan extension is non-additive with 0.5% glucose restriction [14724176]. | Budding yeast |
| OSH7 | OxySterol binding protein Homolog 7 | Overexpression of OSH7 extends mean replicative lifespan. PERG6-OSH7 does not extend the maximum lifespan significantly [Xia et al., unpublished].
Deletion of the CC domain of Osh7 (Perg6-OSH7-ORD) greatly shortens the lifespan. Deletion of the Osh7's CC domain decreases lifespan (Perg6-OSH7-ORD) shortens the lifespan [Tang et al., personal communication].
Osh7 interacts with the late endosome ATPase Vps4 by their C-terminal coiled-coil (CC) domain. | Budding yeast |
| SSD1 | Suppressor of SIT4 Deletion 1 | Overexpression of SSD1 (addition of a SSD1-V allele) increases replicative lifespan by 50%, independently of SIR2 and SIR2 further extends the lifespan, although SIR2 is necessary for SSD1-V cells to attain maximal lifespan [15126388]. SSD1-V also dramatically increases chronological lifespan with lifespan twice as long as ssd1-d cells [19570907]. Deletion of SSD1 increases replicative lifespan by 50% [Li et al., 2009].
Addition of SSD1-V allele to an ssd1-d strain suppresses the short lifespan of an MPT5 deletion mutant [11805047] and extend wild-type lifespan [Kaeberlein and Guarente, unpublished].
SSD1-V slightly extends the lifespan of swi4 and ccr4 mutant strains and suppresses the temperature sensitive growth phenotype of mpt5, ccr3, swi4, and swi6 single mutants [11805047]. SSD1-V also suppresses the synthetic lethality caused by deletion of MPT5 in combination with a mutation in SWI4, SWI6, or CCR4 [11805047]. SSD1-V suppresses mutations that affect cell wall stability [1545797; 8386319], RNA polymerase III activity [8510644], RNA splicing [10446233], and PKA activity [1848673; 8200529]. | Budding yeast |
| PEP4 | carboxyPEPtidase Y-deficient 4 | 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 [21593793]. PEP4 is not DR-essential [18690010]. | Budding yeast |
| VMA1 | Vacuolar Membrane Atpase 1 | 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].
| Budding yeast |
| VPH2 | Vacuolar pH 2 | 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]. | Budding yeast |
| SOD2 | SuperOxide Dismutase 2 | SOD2 deletion decreases replicative lifespan by 72% [17460215]. SOD2 deletion decreases chronological lifespan [21076178]. Deletion of SOD2 decreases chronological lifespan in wild-type and abolishes chronological lifespan extension in sch9Delta mutants as well as decreases chronological lifespan in cyr1:mTn mutants [12586694]. Combined overexpression of SOD1 and SOD2 extends chronological lifespan by 30% in EG103 strain [12586694].
SOD2 deletion mutants are hypersensitive to oxygen and grow poorly in ethanol [10222047]. | Budding yeast |
| SOD1 | SuperOxide Dismutase 1 | The overexpression of Sods, mitochondrial Sod2 and cytosolic CuZnSod (Sod1), in combination delays the age-dependent reversible inactivation of mitochondrial aconitase, a superoxide-sensitive enzyme, and extends chronological lifespan by 30% [12586694]. Deletion of SOD1 decreases replicative lifespan by 40% [17460215]. Overexpression of SOD1 with CCS1 levuates the level of Cn, Zn-Sod activity and increased chronological lifespan. However overexpression of SOD1 without high cooper or simultonous overexpression of CCS1 shortened both chronological and replicative lifespan [15659212]. Overexpression of SOD1 has no effect on replicative lifespan [10224252]. Deletion of SOD1 shortens replicative lifespan by approximately 40%. The magnitude of the decrease in lifespan does not appear to dependent on oxygen concentration in the atmosphere [12020810]. Deletion of SOD1 shortens replicative lifespan [10547026]. Deletion of SOD1 shortens replicative as well as chronological lifespan [10222047].
Cells with a deletion of SOD1 exhibit a profound defect in entry into and survival during stationary phase (i.e. chronological lifespan) in the W303-B strain [8647826; 10222047], which is partially suppressed by expression of human Bcl-2 [9199172].
Hypersensitivity to oxygene and significantly decreased replicative lifespan of SOD1 deletion can be ameliorated by exogenous ascorbate. If acorbate's negative effects of auto-oxidation are prevented by exchange of medium, ascorbate prolongs mean and maximum replicative lifespan in the atmosphere of air and pure oxygene [15621721].
SOD1 deletion causes sensitivity to hyperoxia as well as methionine and lysine auxotrohies [9199172].
| Budding yeast |
| IME1 | Inducer of MEiosis 1 | Transient overexpression of IME1 resets the replicative lifespan of old cells back to that of young cells [21700873]. | Budding yeast |
| NDT80 | Non-DiTyrosine 80 | Transient overexpression of NDT80 rejuvenates old cells [21700873]. | Budding yeast |
