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
    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
    ESA1 esa1-531 mutant has an even shorter chronological lifespan than PKA1 deletion mutant in both 2% glucose (ad libitum) and water (extreme DR) at 30 degree Celsius, a semipermissive temperature. At the permissive temperature (25 degree Celsius) there is little difference [19303850]. 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
    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
    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
    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
    PNC1 Pyrazinamidase/NiCotinamidase 1 Cells with 5 copies of PNC1 have a 70% longer replicative lifespan which is cancelled out by SIR2 deletion. PNC1 is upregulated under glucose DR [12736687]. Pnc1 reduces cellular nicotinamide levels, a product and noncompetitive inhibitor of Sir2 deacetylation reaction. Overexpression of PNC1 suppresses the effect of exogenously added nicotinamide on Sir2-dependent silencing at HM loci, telomeres and rDNA loci [12736687; 14729974]. Pnc1 catalyses the breakdown of nicotinamide to nicotinate and ammonia [12736687]. Deletion of PNC1 shortens replicative lifespan approximately by 10% [12736687] and largely prevents replicative lifespan extension of 0.5% glucose restriction. 0.5% glucose restriction slightly extends median replicative lifespan (by 10 - 15%) but not maximum replicative lifespan in pnc1Delta [14724176]. PNC1 overexpression suppresses the inhibitory effect of exogenously added NAM on silencing, lifespan, and Hst1-mediated transcriptional repression [14729974]. Increased expression of PNC1 is both necessary and sufficient for replicative lifespan extension by DR and low-intensity stress. Under non-stressing conditions (2% glucose, 30 degree Celsius), a strain with additional copies of PNC1 (5XPNC1) has 70% longer replicative lifespan than the wild-type and some cells live for more than 70 divisions. Neither DR nor heat stress further increase the lifespan of the 5XPNC1 strain [12736687]. PNC1 deletion decreases chronological lifespan [17110466]. Budding yeast
    ERG6 ERGosterol biosynthesis 6 Deletion of ERG6 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
    ERG5 ERGosterol biosynthesis 5 Deletion of ERG5 decreases replicative lifespan by 35% in the a strain [18340043], but increases mean chronological lifespan by 26 - 116% (26, 40, 43, 62, 116) in diploid cells [21447998]. Deletion of ERG5 cancels out the replicative lifespan extension of 0.5% glucose restriction [18690010]. 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
    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
    ATG1 AuTophaGy related 11 ATG1 deletion reduces chronological lifespan by 70% [19302372]. Deletion of ATG1 reduces replicative lifespan by 20% in the alpha strain [18340043]. Budding yeast
    NTH2 Neutral TreHalase 2 Deletion of NTH2 shortens mean chronological lifespan by 39% (at 30 degree Celsus in BY4742) [22783207]. NTH2 mutant cells have elevated trehalose concentration before they enter the non-proliferative stationary growth phase which remained high during the stationary phase. NTH2 deletion cells have no altered ROS levels in pre-quiescent cells [22783207]. Budding yeast
    TPS1 Trehalose-6-Phosphate Synthase 1 Deletion of TPS1 decreases intracellular trehalose concentration and shortens the mean chronological lifespan by 74% (at 30 degree Celsus in BY4742) [22783207]. Budding yeast
    NTH1 Neutral trehalase, degrades trehalose; required for thermotolerance and may mediate resistance to other cellular stresses; may be phosphorylated by Cdc28p Deletion of NTH1 decreases mean replicative lifespan by 15% in the a strain [19030232] and mean chronological lifespan by 30% (at 30 degree Celsus in BY4742) [22783207]. Mutant NTH1 cells have reduced oxidative carbonylation of cellular proteins throughout lifespan. NTH1 mutant cells have elevated trehalose concentration and reduced oxidative carbonylation of cellular proteins before they enter the non-proliferative stationary growth phase which remained high during the stationary phase [22783207]. Budding yeast
    AKR1 AnKyrin Repeat-containing protein 1 Deletion of AKR1 decreases replicative lifespan by 40% in the alpha strain [18340043]. Replicative lifespan decreased by 50% in the alpha strain [19030232]. Budding yeast
    ARP1 Actin-Related Protein 1 Deletion of ARP1 decreases replicative lifespan by 40% in the alpha strain [18340043; 19030232]. Budding yeast
    ATP1 ATP synthase 1 Deletion of ATP1 increases chronological lifespan by up to 50% [17492370], but decreases replicative lifespan by 70% in the alpha strain [18340043]. Budding yeast
    CAT5 CATabolite repression 5 Deletion of CAT5 decreases chronological lifespan by up to 50% [17492370] and also decreases replicative lifespan by 30% in the alpha strain [18340043]. Budding yeast
    CCS1 Copper Chaperone for SOD1 1 Deletion of CCS1 reduces replicative lifespan by 50% [17460215]. Budding yeast
    CHL1 CHromosome Loss 1 CHL1 deletion mutant exhibits a shortened mean and maximum lifespan by 36 and 29%, respectively, as well as hypersensitivity to heat stress. CHL1 may modulate transcriptional silencing in the presence of Sir proteins [16182251]. Budding yeast
    CLA4 CLn Activity dependant 4 Deletion of CLA4 decreases replicative lifespan by 60% in the alpha strain [18340043; 19030232]. Budding yeast
    CYT2 Mutation of CYT2 decreases replicative lifespan by 25% in the alpha strain [18340043; 19030232]. Budding yeast
    Factors are an extension of GenAge and GenDR.

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