| PGA3 | Processing of Gas1p and ALP | Low glucose condition induces expression and activity of plasma membrane NADH coenzyme Q reductase (PGA3). Overexpression of PGA3 extends replicative and chronological lifespan by 20-30% [19239415]. | Budding yeast |
| PMR1 | High affinity Ca2+/Mn2+ P-type ATPase required for Ca2+ and Mn2+ transport into Golgi; involved in Ca2+ dependent protein sorting and processing; mutations in human homolog ATP2C1 cause acantholytic skin condition Hailey-Hailey disease | Deletion of PMR1 increses the replicative lifespan by 40% in the alpha strain and by 15% in the a strain. Overexpression of PMR1 extends the lifespan [21918615]. | Budding yeast |
| HPR1 | HyPerRecombination 1 | Deletion of HPR1 decreases replicative lifespan [11756539] | 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 |
| 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 |
| RPL6A | Ribosomal Protein of the Large subunit 6A | Deletion of RPL6A decrease mean replicative lifespan by 25% in the alpha strain [18340043; 18423200], but increases mean replicative lifespan by 40% in the remade strain. Its deletion non-significantly increases mean replicative lifespan in the ORF collection [22377630]. | 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 |
| 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 |
| 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 |
| 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 |
| YMR018W | — | Deletion of YMR018W increases replicative lifespan by 35% in the alpha strain [18340043]. | 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| SIR2 | Silent Information Regulator 2 | Deletion of SIR2 shortens replicative lifespan by approximately 30%. Integration of a second copy of SIR2 into the wild-type strain leads to an extension of replicative lifespan by around 35% in W303R strain [10521401]. Deletion of SIR2 causes genomic instability at rDNA array [2647300] and shortens replicative lifespan by 50% [11000115]. 0.5% glucose restriction fails to increase the short lifespan of sir2Delta [11000115] probably duo to hyperaccumulations of extrachromosomal rDNA circles (ERCs) [16311627]. 0.1% glucose restriction extends replicative lifespan of sir2 mutants [12213553]. 0.5, 0.1 and 0.05% glucose restriction are able to increase lifespan of sir2;fob1 double mutant to a greater extent than in wild-type [15328540]. 0.05% glucose restriction further extends replicative lifespan of SIR2 overexpression mutant [15328540]. Sir2 blocks extreme chronological lifespan extension as the lack of Sir2 along with DR and/or mutations in the yeast AKT homolog, Sch9, or Ras pathways causes a dramatic chronological lifespan extension (6-fold) [16286010]. Sir2 inhibits formation of ERCs and acts on histones as well metabolic enzymes among others. Overexpression extends replicative lifespan in several strains, but not in PSY316 [15684413].
Chronological lifespan of sir2 deletion mutant is significantly extended compared with wild-type in water (extreme DR) but not in saturated cultures containing 2% glucose (ad libitum).
SIR2 mutants are defective for telomere [1913809] and HM silencing [6098447; 3297920]. have increased rDNA recombination [2647300] and a loss of rDNA silencing [9009207; 9009206].
| Budding yeast |
