Interventions

  • name effect species mean median maximum
    RTG3 deletion RTG3 deletion mutation causes an increase in mean replicative in lifespan by 55% increase at 2% glucose, suggesting that expression of genes regulated by Rtg1-Rtg3 has a negative effect on longevity in 2% glucose (in YPK9). A null mutant has 123% increased mean lifespan at 0.1% glucose relative to a wild-type strain at 2% glucose, indicating that reduced glucose and an RTG3 mutation have an additive effect on lifespan (in YPK9) [11024000]. RTG3 null mutant cannot grow on acetate medium and requires glutamate or aspartate for growth [9032238]. Yeast +55
    GTR1 deletion 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]. Yeast -36 -51
    DAP2 deletion 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]. Yeast -19 -36
    SLM4 deletion SLM4 deletion blocks replicative lifespan extension by moderate DR, but does not affect lifespan on AL significantly [22912585]. Yeast +2 -10
    BRE5 deletion Deletion of BRE5 increases mean replicative lifespan by 30% [16293764] and mean chronological lifespan in diploid cells [21447998] Yeast +30
    ATG10 deletion ATG10 deletion cancels out replicative lifespan extension by DR [18690010]. Yeast
    SCP1 deletion Increasing actin dynamics by deletion of SCP1, encoding an actin bundling protein, increases replicative lifespan by 67% as well as chronological lifespan by 88% [15024029]. Yeast +67 to +88
    ATG11 deletion ATG11 deletion extends replicative lifespan under AL and abrogates DR-lifespan extension [18690010]. Yeast
    FKH1 FKH2 deletion 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 a slight increased chronological and replicative lifespan as well as stress resistance [22438832]. Yeast
    SGS1 mutation Deletion of SGS1 causes premature aging including a shortened replicative lifespan by approximately 60%, sterility, fragmentation of the nucleolus and redistribution of the Sir3 silencing protein from telomeres to the nucleolus [Sinclair et al, 1997]. Mutation in SGS1 shortens replicative lifespan by 30% [11290710]. Introduction of mutant allele with a point mutation (SGS1 K(706)-->A) in the RecQ helicase domain that eliminates the DNA helicase activity of Sgs1 fails to rescue the premature aging of the sgs1Delta strain, demonstrating that Sgs1 DNA helicase activity is required for a normal lifespan [11861900]. Most cell death in sgs1 mutant cells is caused by a stochastic cell cycle arrest that is associated with a large-budded terminal morpholgy [McVey et al, 2001]. Overexpression of SIR2 or deletion of FOB1 extend lifespan of only those sgs1 cells that escape this arrest [11290710; 10230397]. sgs mutants have greater rate of telomere loss than wild-type cells in the abscence of telomerase [11179234]. Yeast -60
    ADE4 deletion ade4 mutation extends chronological lifespan, but not replicative lifespan, and is non-additive with 0.5% glucose or amino-acid DR on chronological lifespan extension. ADE4 deletion in atg16 mutants results only in a partial extension of the chronological lifespan by 0.5% glucose DR [20421943]. Yeast
    SWH1 deletion 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]. Yeast
    SIM1 deletion Disruption of SIM1 shortens mean (87.5%), but not maximum, lifespan without causing any other gross changes in cell cycle parameter or growth characteristics [8810036]. Cells bearing deletions in CLB1-4 are unable to undergo mitosis and normally arrest in G2. SIM1 disruption in clb1-4 mutant backgrounds will allow a second round of DNA synthesis without mitosis [8574583]. sim1delta;uth1delta double mutants exhibit various defects, including binucleated cells, benomyl sensitivity, heat shock sensitivity, inability to store glycogen, sensitivity to starvation and failure of spores to germinate [10612745]. Yeast
    SRX1 deletion 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]. Yeast +15 to +20
    CCR4 deletion Deletion of CCR4 increases mean chronological lifespan by 20 - 41% (20, 33, 41) in diploid cells [21447998]. In W303R CCR4 deletion shortens replicative lifespan by approximately 80% and results in temperature sensitivity that is suppressed by SSD1-V. SSD1-V partially suppresses the short-lifespan of ccr4 mutant. CCR4 mutation is synthetically lethal in combination with deletion of MPT5 in the absence of SSD1-V [11805047]. Yeast -80 to +20
    TCO89 deletion TCO89 deletion increases chronological lifespan, increases mitochondrial oxygen consumption, but decreases mitochondrial and cellular ROS in early stationary phase [21641548]. Deletion of TCO89 cancels out replicative lifespan extension by moderate DR [18690010]. Yeast
    SIP1 deletion Deletion of SIP1 decreases replicative lifespan by 80%, without accompying aging biomarkers in S288C strain [10921902]. Yeast -80
    TSA1 activating mutation A gain-of-function allele of peroxiredoxin (thioredoxin peroxidase, Tsa1) causes a dominant oxidative stress-resistance and robust premature aging phenotype with reduced mean lifespan. These effect is not provoked by altered Tsa1 levels, nor can it be stimulated by deletion, haploinssufficiency or overexpression of wild-type allele [20729566]. Yeast
    CDC25 mutation 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]. Yeast +34 +18
    TSA1 deletion Disruption of TSA1 shortens chronological lifespan [15129730]. Replicative lifespan extension by DR in sir2;fob1 double mutant is reduced by TSA1 deletion mutant. Wild-type cells require TSA1 to fully extend lifespan. Mutation in CDC35 (adenylate cyclase), a genetic mimetic of DR, is dependent on TSA1 to extend lifespan [21884982]. Yeast
    CDC6 mutation The CDC6-1 conditional allele results in an approximately 20% increase in mean replicative life span. This allele is defective for replicative initiation form the rDNA ARS at 27 degree Celsius, resulting in a reduced rate of extrachromosomal rDNA circle accumulation [9428525]. The cdc6-1 allele results in genomic instability at the permissive temperature [8552037]. Yeast +20
    ABP1 deletion ABP1 deletion increases replicative lifespan by 30% in the alpha strain and decreases replicative lifespan by 20% in the a strain [18340043]. Deletion of ABP1 increases replicative lifespan by 20% in the alpha strain and decreases replicative lifespan by 20% in the a strain [19030232]. Yeast -20 to +30
    YPT7 deletion YPT7 deletion decreases replicative lifespan by 15% in the alpha strain [18340043]. Deletion of YPT7 cancels out replicative lifespan extension of 0.5% glucose restriction and results under DR also into a shorter replicative lifespan than under AL [18690010]. Yeast -15
    HPR1 deletion Deletion of HPR1 decreases replicative lifespan [11756539] Yeast
    SIR2 mutation Deletion of SIR2 shortens replicative lifespan by approximately 30%. 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]. 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 [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]. Yeast -30
    Interventions are an extension of GenAge and GenDR.