| 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 |
| GPA2 | G Protein Alpha subunit 2 | Deletion of GPA2 increases mean and maximum replicative lifespan by 40% and 26%, respectively [11000115]. Deletion of GPA2 extends replicative lifespan by reducing cAMP-PKA activity and provides a genetic model for DR [11000115]. | 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 |
| 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 |
| GSH1 | glutathione (GSH) 1 | Deletion of GSH1 confers deficiency in glutathione biosynthesis and further increases chronological lifespan under 0.5% glucose restriction, but does not extend chronological lifespan under 2% glucose [18840459]. Therefore, GSH1 has a positive interaction with DR [18840459]. | Budding yeast |
| GUP1 | Glycerol UPtake 1 | GUP1 deletion extends mean and maximum replicative lifespan by 32 and 30%, respectively, as well as chronological lifespan. DR-induced maximal replicative lifespan extension is not further increased by GUP1 deletion, while gup1 mutant displayed longer chronological lifespan under DR [21584246]. | 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| HXT17 | HeXose Transporter 17 | HXT17 mutation extends both replicative and chronological lifespan as well as cancels out DR-induced replicative and chronological lifespan extension. Mean and maximum replicative lifespan are extended by 27 and 49%, respectively [21584246]. | Budding yeast |
| HHF1 | Histone H Four 1 | HHF1 deletion extends mean and maximum replicative by 45 and 69%, respectively, as well as chronological lifespan. Chronological lifespan extension by HHF1 deletion and DR is non-synergistic. DR appears to extend replicative lifespan more when combined with hhf1 mutation, whereas DR does not change hhf1-induced replicative lifespan extension, suggesting a positive interaction [21584246]. | Budding yeast |
| HST1 | Homolog of SIR Two (SIR2) 1 | Deletion of HST1 blocks the residual replicative lifespan extension by hxk2 mutant in a sir2;fob1;hst2 triple mutant background [16051752]. However, DR can increases the replicative lifespan to a similar extent in sir2;fob1;hst1;hst2 quadruple mutant cells as in sir2;fob1 double mutant cells under 0.5, 0.05 and 0.005% glucose conditions and even by hxk2 deletion mutant [16741098; 17129213]. | 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 |
| HES1 | Homologous to kES1 1 | Deletion of HES1 (alias OSH5) extends replicative lifespan and is non-additive with moderate DR. Elevation of OSH5 levels by an ERG6 promoter reduces mean, median and maximum replicative lifespan by 25, 18 and 29%. HES1 is required for the longevity effect of DR, Perg6-OSH6, Perg6-ERG2 and Perg6-OSH7 (genetic mimetics of DR). Hes1 is upregulated in response to sterol down-regulation including DR. Deletion of OSH5 delays different steps of endocytosis, a sterol-requireing process [Xia et al., unpublished].
Perg6-OSH6 osh5 double mutant have a lifespan significantly shorter than that of Perg6-OSH6 [Xia et al. upublished]. | 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 |
| LCB4 | Long-Chain Base 4 | Deletion of LCB4 increases replicative lifespan and cancels out replicative lifespan extension of 0.5% glucose DR [18690010]. | 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 |
| 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 |
| NYV1 | New Yeast V-SNARE 1 | Deletion of NYV1 cancels out replicative lifespan extension of 0.5% glucose restriction and results under DR also into a shorter replicative lifespan than under AL [18690010; 22622083]. Thus, NYV1 deletion blocks DR-lifespan prolongation [18690010].
| 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 |
