| YHB4 | Yeast HemogloBin-like protein 4 | sfa1;yhb1 double mutant cancels out the ability of moderate DR to extend replicative lifespan, but not chronological lifespan. Indicating that NO homeostasis during DR-induced replicative lifespan extension is crucial. Deleting YHB1 partially abolished DR-induced replicative lifespan extension, whereas deleting SFA1 alone had no effect. Yhb1 and Sfa1 may play redundant roles [21584246]. | Budding yeast |
| SFA1 | Sensitive to FormAldehyde 1 | sfa1;yhb1 double mutant cancels out the ability of moderate DR to extend replicative lifespan, but not chronological lifespan. Indicating that NO homeostasis is crucial during DR-induced replicative lifespan extension. Deleting YHB1 partially abolishes the DR-induced replicative lifespan extension, whereas deleting SFA1 alone had no effect. Yhb1 and Sfa1 may play redundant roles [21584246]. | Budding yeast |
| ATG10 | AuTophaGy related 10 | ATG10 deletion cancels out replicative lifespan extension by DR [18690010]. | Budding yeast |
| ATG11 | AuTophaGy related 11 | ATG11 deletion extends replicative lifespan under AL and abrogates DR-lifespan extension [18690010]. | Budding yeast |
| FKH1 | ForK head Homolog 1 | Deletion of FKH1 or FKH2 has no effect on neither replicative, nor chronological lifespan [18225956]. Deletion of both FKH1 and FKH2 reduces mean chronological lifespan by 50% and abrogates lifespan extension and increased stress resistance conferred from water starvation (extreme DR). Modest increase in FKH1 or FKH2 expression results in a slight increased chronological and replicative lifespan as well as stress resistance [22438832]. | Budding yeast |
| FKH2 | ForK head Homolog 2 | Deletion of FKH1 or FKH2 has no effect on neither replicative, nor chronological lifespan [18225956]. Deletion of both FKH1 and FKH2 reduces mean chronological lifespan by 50% and abrogates lifespan extension and increased stress resistance conferred from water starvation (extreme DR). Modest increase in FKH1 or FKH2 expression results in slight increased chronological and replicative lifespan as well as stress resistance [22438832]. | Budding yeast |
| ADE4 | ADEnine requiring 4 | ade4 mutation extends chronological lifespan, but not replicative lifespan, and is non-additive with 0.5% glucose or amino-acid DR on chronological lifespan extension. ADE4 deletion in atg16 mutants results only in a partial extension of the chronological lifespan by 0.5% glucose DR [20421943]. | Budding yeast |
| SRX1 | SulfiRedoXin 1 | Extra copy of SRX1 counteracts age-related hyperoxidation of Tsa1 and extends replicative lifespan by 15 - 20% in a TSA1-dependent manner. Replicative lifespan extension in sir2;fob1 double mutant by DR is reduced by SRX1 deletion. Wild-type cells require SRX1 to fully extend lifespan. DR fails to further extend replicative lifespan of cells carrying an extra copy of SRX1. Mutation in CDC35 (adenylate cyclase), a genetic mimetic of DR, is dependent on SRX1 to extend replicative lifespan [21884982]. | Budding yeast |
| TCO89 | Tor Complex One | TCO89 deletion increases chronological lifespan, increases mitochondrial oxygen consumption, but decreases mitochondrial and cellular ROS in early stationary phase [21641548]. Deletion of TCO89 cancels out replicative lifespan extension by moderate DR [18690010]. | Budding yeast |
| TSA1 | Thiol-Specific Antioxidant 1 | A gain-of-function allele of peroxiredoxin (thioredoxin peroxidase, Tsa1) causes a dominant oxidative stress-resistance and robust premature aging phenotype with reduced mean lifespan. These effect is not provoked by altered Tsa1 levels, nor can it be stimulated by deletion, haploinssufficiency or overexpression of wild-type allele [20729566]. Disruption of TSA1 shortens chronological lifespan [15129730]. Replicative lifespan extension by DR in sir2;fob1 double mutant is reduced by TSA1 deletion mutant. Wild-type cells require TSA1 to fully extend lifespan. Mutation in CDC35 (adenylate cyclase), a genetic mimetic of DR, is dependent on TSA1 to extend lifespan [21884982]. | Budding yeast |
| YPT7 | Yeast Protein Two 7 | YPT7 deletion decreases replicative lifespan by 15% in the alpha strain [18340043]. Deletion of YPT7 cancels out replicative lifespan extension of 0.5% glucose restriction and results under DR also into a shorter replicative lifespan than under AL [18690010]. | Budding yeast |
| VAM7 | VAcuolar Morphogenesis 7 | VAM7 deletion decreases replicative lifespan under AL and blocked DR-mediated lifespan extension. Replicative lifespan decreases by 70% on DR in VAM7 deletion mutant [18690010]. | Budding yeast |
| PNC1 | Pyrazinamidase/NiCotinamidase 1 | Cells with 5 copies of PNC1 have a 70% longer replicative lifespan which is cancelled out by SIR2 deletion. PNC1 is upregulated under glucose DR [12736687]. Pnc1 reduces cellular nicotinamide levels, a product and noncompetitive inhibitor of Sir2 deacetylation reaction. Overexpression of PNC1 suppresses the effect of exogenously added nicotinamide on Sir2-dependent silencing at HM loci, telomeres and rDNA loci [12736687; 14729974]. Pnc1 catalyses the breakdown of nicotinamide to nicotinate and ammonia [12736687]. 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 overexpression suppresses the inhibitory effect of exogenously added NAM on silencing, lifespan, and Hst1-mediated transcriptional repression [14729974]. Increased expression of PNC1 is both necessary and sufficient for replicative lifespan extension by DR and low-intensity stress. Under non-stressing conditions (2% glucose, 30 degree Celsius), a strain with additional copies of PNC1 (5XPNC1) has 70% longer replicative lifespan than the wild-type and some cells live for more than 70 divisions. Neither DR nor heat stress further increase the lifespan of the 5XPNC1 strain [12736687]. PNC1 deletion decreases chronological lifespan [17110466]. | Budding yeast |
| PKH2 | Pkb-activating Kinase Homolog 2 | PKH2 deletion increases replicative lifespan by 20% in the alpha strain and by 15% in the a strain [18340043]. Deletion of PKH2 increases chronological lifespan by 29% [22319457] to 34% [21447998] as well as by 19 - 54% (19, 24, 29, 54) in diploid cells [21447998]. PKH2 mutation extends both replicative and chronological lifespan as well as cancels out DR-induced replicative and chronological lifespan extension [21584246]. Mean and maximum replicative lifespan on AL is extended by 38 and 69%, respectively. | Budding yeast |
| NPT1 | Nicotinate PhosphoribosylTransferase 1 | 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].
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]. | 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 |
| 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 |
| LAT1 | — | LAT1 is suggested to play a role in lifespan extension of DR. Deleting LAT1 abolishes replicative lifespan extension induced by 0.5% and 0.05% glucose restriction. In contrast, overexpressing Lat1 extends replicative lifespan, and this lifespan extension was not further increased by 0.5% glucose restriction. Similar to DR, replicative lifespan extension by LAT1 overexpression largely requires mitochondrial respiration [17200108]. Overexpressing LAT1 extends lifespan (20% mean lifespan increase) and this lifespan extension is not further increased by DR. Similar to DR, lifespan extension by Lat1 overexpression largely requires mitochondrial respiration indicating mitochondrial metabolism plays an important role in DR. Interestingly, LAT1 overexpression does not require the Sir2 family to extend lifespan. Lat1 is also a limiting longevity factor in non-dividing cells in that overexpressing LAT1 extends cell survival during prolonged culture at stationary phase. | Budding yeast |
| IPK1 | Inositol Polyphosphate Kinase 1 | Deletion of IPK1 increases mean replicative lifespan by 41 - 40% in the alpha strain [16293764; 19030232]. IPK1 deletion extends mean and maximum replicative lifespan by 24 and 19%, respectively, and was non-synergistic with moderate DR [21584246]. | 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 |
| GIS1 | GIg1-2 Suppressor 1 | Deletion of GIS1 increases replicative lifespan by 25% in the alpha strain [19030232] and causes major although not complete reversion of chronological lifespan extension by 0.5% glucose restriction [18225956]. | Budding yeast |
| ERG6 | ERGosterol biosynthesis 6 | Deletion of ERG6 cancels out replicative lifespan extension of 0.5% glucose DR and results under DR also into a shorter replicative lifespan than under AL [18690010].
| Budding yeast |
| ERG5 | ERGosterol biosynthesis 5 | Deletion of ERG5 decreases replicative lifespan by 35% in the a strain [18340043], but increases mean chronological lifespan by 26 - 116% (26, 40, 43, 62, 116) in diploid cells [21447998]. Deletion of ERG5 cancels out the replicative lifespan extension of 0.5% glucose restriction [18690010]. | Budding yeast |
