| AVT1 | Amino acid Vacuolar Transport 1 | Overexpressing or deleting AVT1 is sufficient to extend or shorten replicative lifespan, respectively [23172144].
Overexpression of AVT1 prevents mitochondrial dysfunction, prevents alterations in mitochondrial structure and ΔΨ of aged cells even through the vacuolar acidity is reduced in these cells. AVT1 overexpression extends the mean, median and maximum replicative lifespan by 28, 28, and 22%, respectively [23172144].
Deletion of AVT1 accelerates the development of age-induced mitochondrial dysfunction without effecting the kinetics of vacuolar acidity decline and prevents the suppression of mitochondrial dysfunction by VMA1 and VPH2 overexpression without affecting vacuolar acidity. AVT1 deletion decreases mean, median and maximum replicative lifespan by 21, 22, and 12%, respectively [23172144]. | Budding yeast |
| VMA1 | Vacuolar Membrane Atpase 1 | Overexpression of VMA1 increases vacuolar acidity and suppresses age-induced mitochondrial dysfunction of aged cells (17 or 18 cell divisions) which requires the V-ATPase activity. VMA1 overexpression significantly increases mean, median and maximum lifespan by 39 - 45%, 39 - 48% and 50 - 60%, respectively. DR (0.5% glucose restriction) does not further increase the lifespan of VMA1 overexpression strain [23172144].
| 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 |
| 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 |
| VPS21 | Vacuolar Protein Sorting 21 | Lack of VPS21 reduces lifespan under starvation conditions to a level similiar to that of wild-type cells incubated in synthetic complete medium and therefore blocked the lifespan-extending effect of DR [20657825]. | Budding yeast |
| VPS8 | Vacuolar Protein Sorting 8 | Lack of VPS8 reduces lifespan under starvation conditions to a level similiar to that of wild-type cells incubated in synthetic complete medium and therefore blocked the lifespan-extending effect of DR [20657825]. | 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 |
| 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 |
| PCK1 | Phosphoenolpyruvate CarboxyKinase 1 | Loss of Pck1 activity blocks chronological lifespan extension caused by water starvation. Knockout of PCK1 dramatically reduces chronological lifespan in both water (extreme DR) and glucose-containing medium. pck-1-K514Q mutation which abrogates enzymatic activity of Pck1, just like SIR2 deletion, extends chronological lifespan in water. Deletion of SIR2 does not alter the lifespan of PCK1 deletion mutant, pck1-K514R, and pck1-K514Q mutants [19303850]. | 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 |
| ERG3 | ERGosterol biosynthesis | Deletion of ERG3 decreases replicative lifespan under AL, 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 |
| SUR4 | SUppressor of Rvs161 and rvs167 mutations 4 | Deletion of SUR4 cancels out replicative lifespan extension of 0.5% glucose DR [18690010]. | 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 |
| 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 |
| NFU1 | NifU-like protein 1 | NFU1 mutation slightly shortens the chronological lifespan under AL and the chronological lifespan of NFU1 mutants is not extended by 0.5% glucose DR [20421943]. | Budding yeast |
| FET3 | FErrous Transport 3 | FET3 mutation slightly shortens chronological lifespan under AL. Its chronological lifespan is not extended by 0.5% glucose or amino-acid DR [20421943]. FET3 is one of several iron related genes that are up-regulated in response to increasing strength of glucose DR [18679056]. | Budding yeast |
| ATG16 | AuTophaGy related 16 | Under AL atg16 mutation shortens chronological, but not replicative lifespan. 0.5% glucose DR extends chronological lifespan of atg16 mutants, but amino-acid DR does not extend the short chronological lifespan of atg16 mutants (similar to several other autophagy mutants). ADE4 deletion in atg16 mutants results only in a partial extension of chronological lifespan by 0.5% glucose DR. The long chronological lifespan of tor1 mutants requires ATG16 [20421943]. | Budding yeast |
| ATG2 | AuTophaGy related 2 | ATG2 deletion prevents chronological lifespan extension induced by amino-acid DR [20421943]. | Budding yeast |
| VPS30 | Vacuolar Protein Sorting 30 | VPS30 deletion prevents chronological lifespan extension induced by amino-acid DR [20421943]. | 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 |
| 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 |
| AIM4 | Altered Inheritance rate of Mi 4 | AIM4 (alias SOY1) deletion increases chronological and replication lifespan, which is non-additive with DR. On AL mean and maximum replicative lifespan are extended by 63 and 69%, respectively. DR appears to decrease aim4-induced replication lifespan extension, indicating a negative interaction. aim4 mutation does not change DR-induced chronological lifespan extension [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 |
| 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 |
