| LAG2 | Protein involved in determination of longevity | Deletion of LAG2 in haploid SP1 strain does not affect growth, but results in a 50% decrease in the mean and maximum replicative lifespan. When LAG2 is overexpressed, the mean and maximum replicative lifespan is extended by about 36% and 54%, respectively. Overexpression induced at generation 12 similarly increases replicative lifespan [8760941]. | Budding yeast |
| HST2 | Homolog of SIR Two (SIR2) 2 | HST2 overexpression extends replicative lifespan. 0.5% glucose restriction does not increase lifespan of sir2;fob1;hst2 triple mutants [16051752]. DR increases lifespan of all four sir2;fob1;hstX(X = sirtuin) triple mutants [16741098; 17129213]. | Budding yeast |
| HAP4 | Heme Activator Protein 4 | Overexpression of HAP4 from the ADH1 promoter extends lifespan of PSY316 strain approximately 40% under growth conditions favoring fermentation (2% glucose). Overexpression of HAP4 increases replicative lifespan, but is non-additive with 0.5% glucose restriction in lifespan extension. Lifespan extension by HAP4 overexpression requires SIR2 [12124627]. HAP4 deletion suppresses replicative lifespan extension to 30% and 33% on 0.1% glucose and on elimination of non-essential amino acids, respectively [20178842]. HAP4 overexpressing cells demonstrate a transcriptional response resembling cells undergoing diauxic shift, consume more oxygen, and exhibit increased Sir2-dependent transcriptional silencing at telomeres and rDNA [12124627]. | Budding yeast |
| GUT2 | Glycerol UTilization 2 | Overexpression of GUT2 extends replicative lifespan by 25% and does not synergize with 0.5% glucose restriction [18381895]. | Budding yeast |
| AAT1 | Aspartate AminoTransferase 1 | Overexpression of AAT1 extends replicative lifespan by 25% and does not synergize with 0.5% glucose restriction [18381895]. | Budding yeast |
| TLC1 | — | Overexpression of a truncated allele of TLC1 abrogates telomere silencing [7545955], shortened telomeres and extends replicative lifespan approximately by 20% [9275199]. Deletion of TLC1 might decrease replicative lifespan [Nugent et al., 1996].
| 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 |
| 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 |
| MXR1 | peptide Methionine sulfoXide Reductase 1 | Deletion of MXR1 (alias MsrA) decreases by 25% and overexpression slightly increases the replicative lifespan [15141092]. Deletion of MXR1 decreases replicative lifespan [19049972]. MXR1 deletion decreases replicative lifespan on either glucose or lactate as carbon source [20799725]. Although deletion or overexpression of MXR2 (alias MsrB) has no effect under normal growth conditions, the simultaneous deletion of MXR1 and MXR2 reduces the lifespan by 63% [15141092]. | Budding yeast |
| 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 |
| FIS1 | fission 1 (mitochondrial outer membrane) homolog (S. cerevisiae) | 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]. | Budding yeast |
