| BMH1 | Brain Modulosignalin Homologue 1 | Deleting BMH1 extends chronological lifespan by 25% and is associated with activated stress response, decreased ROS levels and increased heat-shock-element-driven transcription activity. BMH1 deletion was non-additive with the genetic DR mimetic cdc25 and tor1. Water starvation (a form of extreme DR) extends chronological lifespan of BMH1 mutant even more as it does in wild-type. BMH1 genetically interacts with DR as well as TOR- and PKA-signaling pathways to regulate lifespan. Phosphorylation of Ser238 on Bmh1 increases during chronological aging, which is delayed by DR or reduced TOR activity [19805817].
| Budding yeast |
| ATG15 | AuTophaGy related 15 | Deletion of ATG15 does not affect the lifespan significantly on AL, while DR shortens replicative lifespan of ATG15 deletion mutant by 28% [18690010]. | 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 |
| TOR1 | Target Of Rapamycin 1 | TOR1 deletion extends mean and maximum replicative lifespan by 21 and 25% [16293764] as well as chronological lifespan [21076178]. This lifespan extension is independent of SIR2 and additive with deletion of FOB1 [16293764]. Deletion of TOR1 fails to increase the replicative lifespan of a sir2 mutant [20947565]. Deletion of TOR1 substantially extends chronological lifespan, increasing median survival almost 3-fold (wild-type 4.5 days, tor1 null 12 days), i.e. by 167%. By 21 days in culture, the vast majority of wild-type cells had died (>99.9%), whereas many tor1 null cells remained viable. Deletion of TOR1 also extends the chronological lifespan of the relatively short-lived BY4742 strain, one of the two haploid genetic backgrounds of the widely used Yeast Knockout Collection available from Open Biosystems. Deletion of TOR1 fails to extend chronological lifespan in Petite strains that are unable to respire [17403371]. TOR1 deletion increases replicative lifespan by 30% in the alpha strain and 20% in a strain [19030232]. TOR1 deletion mutant have and increased mean and maximum replicative lifespan by 21% and 6%, respectively [21931558]. Deletion of TOR1 extends replicative lifespan as well as chronological lifespan [21076178] and glucose restriction fails to further extend the long replicative lifespan of tor1Delta [16293764; 16418483; 18225956]. Water starvation (extreme DR) further extends chronological lifespan of tor1 mutants [18225956]. | Budding yeast |
| SCH9 | — | Transposon-mediated mutagenesis of SCH9, which encodes for a serine threonine kinase homologous to Akt/PKB, increases resistance to oxidants and thermal stress as well as extends chronological lifespan by 30%. SCH9 deletion increases chronological lifespan by up to threefold. Stress-resistance transcription factors Msn2/Msn4 and protein kinase Rim15 are required for this life-extension. Deletion of the mitochondrial antioxidant enzyme superoxide dismutase gene SOD2 prevents the increased chronological lifespan caused by SCH9 deletion [11292860]. Mutations that decrease the activity of the Ras/Cyr1/PKA pathway also extend longevity and increase stress resistance by activating transcription factors Msn2/Msn4 and Sod2 [12855292]. SCH9 deletion mutants exhibit more than 3-fold extension of chronological lifespan. By day 9 of medium depletion all the wild-type cells were dead while 50% sch9 mutants survived [17710147]. Deletion of SCH9 also increases resistance to heat shock and oxidative stress [11292860], and increases replicative lifespan by 18% (in DBY746) [12586694]. SCH9 deletion increases the replicative lifespan by 40% in the alpha strain [18340043] and increases mean chronological lifespan by 97 - 246% (97, 133, 154, 226, 246) in diploid cells [21447998]. Mutation or deletion of SCH9 increases resistance to oxidants and extends chronological lifespan [11292860; 16286010]. The extended lifespan of SCH9 deletion mutants is not further extended by low glucose DR and is independent of Sir2 [16293764]. Deletion of RIM15 or GIS1 reverses chronological lifespan extension associated with sch9Delta. Water restriction further increases chronological lifespan of sch9Delta [18225956]. Deletion of SCH9 results in a longer chronological lifespan [21076178]. | Budding yeast |
| RPL31A | Ribosomal Protein of the Large subunit 31A | Deletion of RPL31A increases mean replicative lifespan by 45% [16293764]. Mean replicative lifespan increases by 35% in the alpha strain and 50% in a strain [19030232; 18423200]. Mean replicative lifespan of the RPL31A deletion mutant increases by 35% in the ORF collection and by 29% in the remade strain [22377630]. RPL31A deletion increases significantly replicative lifespan [17174052]. Deletion of RPL31A extends replicative lifespan and is not further extended by 0.05% glucose restriction [18423200]. | Budding yeast |
| RPD3 | Reduced Potassium Dependency 3 | Deletion of the histone deacetylase gene RPD3 extends lifespan by 41%, independently of an intact Sir silencing complex (in the short lived YSK661 strain) [10512855]. Deletion of RPD3 extends replicative lifespan and there was no additive effect by neither 0.1% glucose nor amino acid restriction [12213553].
RPD3 deletion increases rDNA silencing in a partially SIR2-dependent manner [10082585].
Its effects on chromatin functional state were evidenced by enhanced silencing at the three known heterochromatic regions in the genome, the silent mating type (HM), subtelomeric, and rDNA loci, which occurred even in the absence of SIR3 [10512855]. | Budding yeast |
| RIM15 | Regulator of IME2 15 | RIM15 deletion results in 50% reduction of maximal chronological lifespan [11292860] and consistently decreases chronological lifespan under AL [21076178]. Rim15 is required for chronological lifespan extension caused by deficiency in RAS2, TOR1, or SCH9, as well as by 0.5% glucose restriction, but not by water starvation [18225956]. | Budding yeast |
| RAS2 | Ras-like protein 2 | Overexpression of RAS2 causes a 43% increase in mean and 18% increase in maximum lifespan as well as postpones the age-related increase in generation time. RAS2 deletion causes a 23% decrease in mean and a 30% decrease in maximum lifespan [8034612]. Deletion of RAS2 leads to a longer chronological lifespan [21076178]. Deletion of the RAS2 gene, which functions upstream of CYR1, doubles the mean chronological lifespan by a mechanism that requires Msn2/4 and Sod2 [12586694]. DR further extends chronological lifespan of ras2Delta [18225956]. | Budding yeast |
| HXK2 | HeXoKinase 2 | Deletion of HXK2 extends mean and maximum replicative lifespan by about 53% and 33%, respectively. Limiting glucose availability by mutating HXK2 significantly extends replicative lifespan and provides a genetically model of DR [11000115]. HXK2 deletion increases oxygene consumption. Changes in gene expression HXK2 mutation are quite similar to those of dietary-restricted cells. In fact, HXK2 mutants have a transcriptional profile that significantly resembles DR cells and cell overexpressing HAP4 [12124627]. | Budding yeast |
| GPR1 | G-Protein coupled Receptor 1 | Deletion of GRP1 increases mean and maximum replicative lifespan by 41% and 26%, respectively. GRP1 deletion mutants have also longer chronological lifespan. Deletion of GPR1 extends replicative lifespan by reducing cAMP-PKA activity and provides a genetically model for DR [11000115]. | Budding yeast |
| CDC25 | Cell Division Cycle 25 | The CDC25-10 allele extends mean and maximum replicative lifespan by 34% and 18%, respectively, at 30 degree Celsius. cdc25-10 mutants have an extended replicative lifespan under AL. Growth on 0.5% glucose restriction does not further extend replicative lifespan of cdc25-10 mutants. CDC25 null mutant is not viable. CDC25 appears to act in the same genetic pathway as SIR2 and NPT1 and is suggested to be genetic model of DR [11000115]. | Budding yeast |
| ATG17 | AuTophaGy related 17 | ATG17 deletion decreases replicative lifespan under AL and blocks DR-lifespan extension. ATG17 mutant's replicative lifespan decreases by 70% on DR [18690010]. | Budding yeast |
| HSP12 | Heat Shock Protein 12 | HSP12 deletion slightly increases mean, medium, and maximum replicative lifespan by 24, 27, and 3% under AL, but totally abolishes the lifespan extending effect of moderate DR [Alan Morgan, personal communication; Herbert et al. in press].
HSP12 encodes a small heat-shock protein which mRNA levels increases in response to diverse environmental stresses (including heat-, osmotic-, and oxidative stress) [11102521; 10722658] and its protein levels are induced upon both DR and high osmolarity. However, HSP12 deletion has no effect on resistance to variety of stresses (including oxidative stress). Hsp12 is monomeric, has negligible in vitro protein chaperone activity, and is intrinsically unstructured/unfolded in water, but switches to a dynamic 4-helical conformation upon membrane binding. These all indicates that Hsp12 has membrane-stabilising "lipid chaperone" functions and while its low levels exerts some negative effects on lifespan high levels of Hsp12 are required for DR-induced lifespan extension [Alan Morgan, personal communication; Herbert et al. in press]. | Budding yeast |
| CYR1 | CYclic AMP Requirement 1 | The CDC35-1 allele of the adenylate cyclase CYR1 confers a 75% extension of replicative lifespan at 25 degree Celsius [11000115]. Transposon-mutagenized CYR1 increases resistance to oxidants and extends chronological lifespan by up to 90%. Stress-resistance transcription factors Msn2/Msn4 and protein kinase Rim15 are required for this lifespan extension [11292860]. CYR1 mutation is assumed to act as genetic DR mimetic [11000115]. The CDC35-1 allele of the adenylate cyclase CYR1 confers a 75% extension of replicative lifespan at 25 degree Celsius [11000115]. cyr1-1 mutation extends median chronological lifespan by 28-47% and is non-addative with lifespan extension conferred by overxpression of human MAPK1 [17662940]. | Budding yeast |
| MXR2 | peptide Methionine sulfoXide Reductase 2 | Deletion or overexpression of MXR2 (alias MsrB) has no effect on replicative lifespan under normal growth conditions. Simulatonous deletion of MXR2 together with MXR1 dramatically reduces replicative lifespan by 63%. Overexpression of MXR2 under DR conditions extends replicative lifespan by 120% [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 |
| MDH1 | Malate DeHydrogenase 1 | Overexpression of MDH1 extends replicative lifespan by 25% and does not synergize with 0.5% glucose restriction [18381895]. | Budding yeast |
| MSN2 | Multicopy suppressor of SNF1 mutation 2 | Deletion of MSN2 and MSN4 extends replicative lifespan and is further extended by cyr1::mTn [14741356]. Deletion of MSN2 and MSN4 does not significantly decrease chronological lifespan under AL, but attenuates chronological lifespan extension by water starvation and 0.5% glucose restriction [18225956] as well as cancels out lifespan extension of cyr1::mTn [14741356] and decreases chronological lifespan extension of ras2 deletion mutant [12586694]. Simultaneous deletion of MSN2 and MSN4 has no effect on chronological lifespan, but prevents lifespan extension by RAS2 deletion [12586694]. msn2 msn4 has no effect on replicative lifespan in PSY316, and does not prevent lifespan extension by DR [11000115] or by high osmolarity [12391171]. | Budding yeast |
| MSN4 | Multicopy suppressor of SNF1 mutation 4 | Deletion of MSN2 and MSN4 extends replicative lifespan and is further extended by cyr1::mTn [14741356]. Deletion of MSN2 and MSN4 does not significantly decrease chronological lifespan under AL, but attenuates chronological lifespan extension by water starvation and 0.5% glucose restriction [18225956] as well as cancels out lifespan extension of cyr1::mTn [14741356] and decreases chronological lifespan extension of ras2 deletion mutant [12586694]. Simultaneous deletion of MSN2 and MSN4 has no effect on chronological lifespan, but prevents lifespan extension by RAS2 deletion [12586694]. msn2 msn4 has no effect on replicative lifespan in PSY316, and does not prevent lifespan extension by DR [11000115] or by high osmolarity [12391171]. | Budding yeast |
| VPS20 | Vacuolar Protein Sorting 20 | VPS20 deletion decreases mean and maximum replicative lifespan by 16% and 19%, respectively, and additionally cancels out the DR-induced replicative lifespan extension [22912585]. | Budding yeast |
| OPT2 | OligoPeptide Transporter 2 | OPT2 deletion increases mean and maximum replicative lifespan by 23 and 9%, respectively, and cancels out the lifespan-extending effect of DR [22912585]. | Budding yeast |
| GTR1 | GTp binding protein Resemblance 1 | GTR1 deletion decreases mean and maximum replicative lifespan under AL by 36 and 51%, respectively, and cancels out the lifespan extending effect of DR [22912585]. | Budding yeast |
| DAP2 | Dipeptidyl AminoPeptidase 2 | DAP2 deletion decreases mean and maximum replicative lifespan under AL by 19 and 36%, respectively, and cancels out the lifespan extending effect of moderate DR [22912585]. | Budding yeast |
| SWH1 | — | SWH1 (alias OSH1) deletion mutants have an extended replicative lifespan (p=0.02) and DR does not increase the long lifespan of SWH1 deletion mutants [Xia et al. unpublished]. | Budding yeast |
