| 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 |
| IDH2 | Isocitrate DeHydrogenase 2 | 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 5, 19 and 15% [23167605]. | 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 |
| INM2 | INositol Monophosphatase 2 | Deletion of INM2 decreases replicative lifespan by 70% in the alpha strain [19030232]. | Budding yeast |
| IPT1 | InositolPhosphoTransferase 1 | Transposon-mediated mutation of IPT1 increases oxidative stress resistance and chronological lifespan by 40% [16527275]. IPT1 deletion decreases replicative lifespan by 30% in the alpha strain [19030232]. | Budding yeast |
| ISC1 | Inositol phosphoSphingolipid phospholipase C 1 | ISC1 deletion decreases chronological lifespan [21707788; 21707788]. CTA1
overexpression partially suppresses the shortened lifespan by ISC1. Deletion of SIT4 totally rescues the short lifespan of ISC1 mutants [21707788]. HOG1 deletion partially suppresses the premature aging phenotype and short lifespan of ISC1 deletion [22445853]. | Budding yeast |
| KES1 | KrE11-1 Suppressor | Deletion of OSH4 decreases mean replicative lifespan by 18% [Xia et al., unpublished]. | Budding yeast |
| KSS1 | Kinase Suppressor of Sst2 mutations 1 | Deletion of KSS1 results in increased sensitivity to heat shock and oxidative stress and a 25% reduction in median chronological lifespan [17662940]. | Budding yeast |
| 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 |
| 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 |
| MDH1 | Malate DeHydrogenase 1 | Overexpression of MDH1 extends replicative lifespan by 25% and does not synergize with 0.5% glucose restriction [18381895]. | Budding yeast |
| MEC1 | Mitosis Entry Checkpoint 1 | MEC1 mutants have a 3-fold reduced mean and maximum chronological lifespan under conditions of medium depletion [17710147]. | 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 |
| MRS4 | Mitochondrial iron transporter of the mitochondrial carrier family (MCF), very similar to and functionally redundant with Mrs3p; functions under low-iron conditions; may transport other cations in addition to iron | MRS4 deletion decreases mean replicative lifespan by 30% in the alpha strain and 40% in a strain [18340043; 19030232]. | Budding yeast |
| MTC5 | Maintenance of Telomere Capping 5 | Deletion of MTC5 decreases replicative lifespan by 35% in the alpha strain [19030232]. | 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 |
| NCA3 | Nuclear Control of ATPase 3 | 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]. | 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 |
| NDT80 | Non-DiTyrosine 80 | Transient overexpression of NDT80 rejuvenates old cells [21700873]. | Budding yeast |
| NMT1 | N-myristoyl transferase, catalyzes the cotranslational, covalent attachment of myristic acid to the N-terminal glycine residue of several proteins involved in cellular growth and signal transduction | 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. | Budding yeast |
| NNT1 | Nicotinamide N-methylTransferase 1 | 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%. 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 overexpression increases rDNA silincing, whereas deletion decreases rDNA silencing. Overexpression of human nicotinamide N-methyltransferase also increases rDNA silencing [12736687]. | 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 |
| NTH1 | Neutral trehalase, degrades trehalose; required for thermotolerance and may mediate resistance to other cellular stresses; may be phosphorylated by Cdc28p | Deletion of NTH1 decreases mean replicative lifespan by 15% in the a strain [19030232] and mean chronological lifespan by 30% (at 30 degree Celsus in BY4742) [22783207].
Mutant NTH1 cells have reduced oxidative carbonylation of cellular proteins throughout lifespan. NTH1 mutant cells have elevated trehalose concentration and reduced oxidative carbonylation of cellular proteins before they enter the non-proliferative stationary growth phase which remained high during the stationary phase [22783207]. | Budding yeast |
| NTH2 | Neutral TreHalase 2 | Deletion of NTH2 shortens mean chronological lifespan by 39% (at 30 degree Celsus in BY4742) [22783207].
NTH2 mutant cells have elevated trehalose concentration before they enter the non-proliferative stationary growth phase which remained high during the stationary phase. NTH2 deletion cells have no altered ROS levels in pre-quiescent cells [22783207]. | Budding yeast |
