Factors

We need to know every factor which determines lifespan.

Lifespan factors often but not always originate from defined genetic elements. They are not just genes, by definition they can be anything for which a Classifications schema can be build for that is related to the regulation of lifespan, such entities may include Single-Nucleotide Polymorphism, transcript variants, proteins and their complexes, compounds (i.e. small molecules like metabolites and drugs), etc. A factor should be based on a defined molecular entity or genomic position and been classified. It shall be highly flexible and scalable Concept.

While individual lifespan factors within each species or precise defined molecular entities will be captured within the Lifespan App, Data Entries of the Data App may summarize for instance the relevance of each factor class (e.g. homologous group; chemical derivate of related structure and properties, etc.) as well as draw overall conclusions. o

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  • symbol name observation species
    YHB4 Yeast HemogloBin-like protein 4 sfa1;yhb1 double mutant cancels out the ability of moderate DR to extend replicative lifespan, but not chronological lifespan. Indicating that NO homeostasis during DR-induced replicative lifespan extension is crucial. Deleting YHB1 partially abolished DR-induced replicative lifespan extension, whereas deleting SFA1 alone had no effect. Yhb1 and Sfa1 may play redundant roles [21584246]. 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
    FRE6 Ferric REductase 6 FRE6 deletion increases mean replicative lifespan by 14% and cancels out the lifespan extending effect of DR [22912585]. Budding yeast
    RCR2 Resistance to Congo Red 2 RCR2 deletion extends mean replicative lifespan by 18% and cancels out the lifespan extending effect of DR [22912585]. Budding yeast
    YDL180W YDL180W deletion impairs DR-mediated replicative lifespan extension, but does not change lifespan on AL significantly [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
    SLM4 Synthetic Lethal with Mss4 4 SLM4 deletion blocks replicative lifespan extension by moderate DR, but does affect lifespan on AL significantly [22912585]. Budding yeast
    ATG10 AuTophaGy related 10 ATG10 deletion cancels out replicative lifespan extension by DR [18690010]. Budding yeast
    ATG11 AuTophaGy related 11 ATG11 deletion extends replicative lifespan under AL and abrogates DR-lifespan extension [18690010]. Budding yeast
    ERG2 ERGosterol biosynthesis 2 Overexpression of ERG2 with the promoter of ERG6 (Perg6-ERG2) extends replicative lifespan and this effect was overlapping with moderate DR, because DR can not extend the lifespan of this mutant [Tang et al., unpublished]. Perg6-ERG2 does not extend the lifespan significantly on normal medium, but it reverses the effect of DR. DR greatly shortens the lifespan of Perg6-ERG2 mutants. Perg6-ERG2 shortens the lifespan of nyv1 deletion mutations [Xia et al. unpublished]. Deletion of OSH5 greatly shortens the lifespan of Perg6-ERG2. SIR2 overxpression extends the lifespan of Perg6-ERG2 [Xia et al. unpublished]. Budding yeast
    FKH1 ForK head Homolog 1 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]. Budding yeast
    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
    ADE4 ADEnine requiring 4 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]. 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
    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
    OSH6 OxySterol binding protein Homolog 6 Elevation of OSH6 levels by an ERG6 promoter extends mean, median and maximum replicative lifespan by 39, 52 and 18% which is non-additive with 0.5% glucose restriction. It also extends the lifespan of NYV1 mutant [Geber et al., unpublished]. The long lifespan of Perg6-OSH6 is not further extended by deletion of TOR1 [22622083]. OSH6 overexpression decreases total cellular sterol content and reduces Lst8 protein levels. The CC domain of Osh6 is dispensable for longevity. Deletion of the CC domain leads Osh6 to the late endosome. [Fusheng Tang, personal communication]. OSH6 deletion does not affect lifespan under normal conditions, but it abrogates the lifespan extension by 0.5% glucose restriction [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
    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
    TCO89 Tor Complex One 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]. Budding yeast
    TSA1 Thiol-Specific Antioxidant 1 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]. 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]. Budding yeast
    YPT7 Yeast Protein Two 7 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]. Budding yeast
    VMA2 Vacuolar Membrane Atpase 2 VMA2 deletion mutants have a reduced ΔΨ and mitochondrial morphology similar to aged cells. The restoration of the vacuolar acidity in daughter cells requires V-ATPase activity as it is eliminated in VMA2 deletion mutant cells [23172144]. VMA2 deletion mutation decreases the mean replicative lifespan by 80% in the alpha strain [18340043]. Deletion of VMA2 decreases mean, median and maximum replicative lifespan by 84%, 84% and 70%, respectively. DR (0.5% glucose restriction) does not extend the replicative lifespan of VMA2 and shortens it even more [23172144]. Budding yeast
    VAM7 VAcuolar Morphogenesis 7 VAM7 deletion decreases replicative lifespan under AL and blocked DR-mediated lifespan extension. Replicative lifespan decreases by 70% on DR in VAM7 deletion mutant [18690010]. 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
    Factors are an extension of GenAge and GenDR.

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