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
    POL1 POLymerase 1 Mutation of POL1 results in a 20-60% reduction in mean lifespan (in SS111) [12024027] Budding yeast
    RAD27 Deletion of RAD27 results in signs of premature aging and approximately 60% reduction in mean replicative lifespan [12024027]. Budding yeast
    RAD51 RADiation sensitive 51 Rad51 mutations result in a 40% reduced mean replicative lifespan in strain PSY316 [10207108]. RAD51 is required for gene conversion, but not for repair of an HO-induced double-stranded break [8692957]. RAD51 deletion decreases formation of extrachromosomal rDNA circles [10207108]. Budding yeast
    RIF1 RAP1-Interacting Factor 1 Deletion of RIF1 decrease replicative lifespan by 40% [9275199]. RIF1 deletion increases telomere silencing and length [8319907; 1577274], and therefore likely recruits SIR2 from rDNA to the telomeres which result in lifespan shortening. The sir4-42 allele suppresses the short lifespan of a RIF1 mutant [9275199]. Budding yeast
    RSR1 RaS-Related 1 Deletion of RSR1 (alias BUD1) shortens replicative lifespan [9789734]. Budding yeast
    SIP1 SNF1-Interacting Protein 1 Deletion of SIP1 decreases replicative lifespan by 80%, without accompying aging biomarkers in S288C strain [10921902]. Budding yeast
    SIR3 Silent Information Regulator 3 Deletion of SIR3 shortens replicative lifespan by approximately 20% [10521401]. SIR3 mutants exhibit a loss of silencing at the silent mating loci [6098447; 3297920] and telomerease [1913809] and have a slighlty elevuated level of rDNA marker loss [10521401]. The lifespan reduction of SIR3 deletion is suppressed by preventing mating type heterozygosity and is therefore probably due to the simultaneous expression of a and alpha mating-type information, which indirectly causes an increase in rDNA recombination and likely increases the production of extrachromosomal rDNA circles [10521401]. Deletion of SIR3 itself has little effect on lifespan, although it markedly accelerates the increase in cell generation time that occurs during aging [10512855]. The S755A allele of SIR3 (which prevents phosphorylation of Sir3) results in a 40% increase in mean and maximum lifespan [12640455]. Budding yeast
    SOD1 SuperOxide Dismutase 1 The overexpression of Sods, mitochondrial Sod2 and cytosolic CuZnSod (Sod1), in combination delays the age-dependent reversible inactivation of mitochondrial aconitase, a superoxide-sensitive enzyme, and extends chronological lifespan by 30% [12586694]. Deletion of SOD1 decreases replicative lifespan by 40% [17460215]. Overexpression of SOD1 with CCS1 levuates the level of Cn, Zn-Sod activity and increased chronological lifespan. However overexpression of SOD1 without high cooper or simultonous overexpression of CCS1 shortened both chronological and replicative lifespan [15659212]. Overexpression of SOD1 has no effect on replicative lifespan [10224252]. Deletion of SOD1 shortens replicative lifespan by approximately 40%. The magnitude of the decrease in lifespan does not appear to dependent on oxygen concentration in the atmosphere [12020810]. Deletion of SOD1 shortens replicative lifespan [10547026]. Deletion of SOD1 shortens replicative as well as chronological lifespan [10222047]. Cells with a deletion of SOD1 exhibit a profound defect in entry into and survival during stationary phase (i.e. chronological lifespan) in the W303-B strain [8647826; 10222047], which is partially suppressed by expression of human Bcl-2 [9199172]. Hypersensitivity to oxygene and significantly decreased replicative lifespan of SOD1 deletion can be ameliorated by exogenous ascorbate. If acorbate's negative effects of auto-oxidation are prevented by exchange of medium, ascorbate prolongs mean and maximum replicative lifespan in the atmosphere of air and pure oxygene [15621721]. SOD1 deletion causes sensitivity to hyperoxia as well as methionine and lysine auxotrohies [9199172]. Budding yeast
    SUN4 Disruption of SUN4 shortens mean (87.5% of normal), but not maximum, replicative lifespan in BKY1-14c [Austriaco, N.R. (1996) “UTH1 and the Genetic Control of Aging in the Yeast, Saccharomyces cerevisiae.” Ph.D. Thesis, Massachusetts Institute of Technology; 8810036] SUN4 mutation causes failure of daughter cells to completely detach and results in a multi-budded morphology [10683261]. Budding yeast
    SWI4 SWItching deficient 4 Deletion of SWI4 shortens replicative lifespan by approximately 90% [11805047]. SSD1-V partially suppresses the short lifespan of a swi4 mutant. Mutation of swi4 results in slow growth and temperature sensitivity, both of which are suppressed by SSD1-V [11805047]. Budding yeast
    SIM1 Start Independent of Mitosis 1 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]. Budding yeast
    ACH1 Acetyl CoA Hydrolase 1 ACH1 deletion cells accumulate a high amount of extracellular acetic acid and display a reduced mean and maximum chronological lifespan. Maximum lifespan is reduced by 32%. Lifespan shortening is completely abrogated by alleviating the acid stress either by a DR regimen that prevents acetic acid production or by transferring chronologically aging mutant cells to water. Deletion of ACH1 is accompanied by reactive oxygen species accumulation, severe mitochondrial damage, and an early insurgence of apoptosis [22754872]. Budding yeast
    YBR225W Deletion of YBR225W decreases replicative lifespan by 40% in the alpha strain [19030232]. Budding yeast
    VMS1 VCP/Cdc48-associated Mitochondrial Stress-responsive 1 Deletion of VMS1 decreases replicative lifespan by 25% in the alpha strain [19030232]. Budding yeast
    RRG1 Deletion of RRG1 decreases replicative lifespan by 50% in the alpha strain [19030232]. Budding yeast
    YDR089W Deletion of YDR089W decreases replicative lifespan by 30% in the alpha strain [19030232]. Budding yeast
    MTC5 Maintenance of Telomere Capping 5 Deletion of MTC5 decreases replicative lifespan by 35% in the alpha strain [19030232]. Budding yeast
    YDR132C Deletion of YDR132C decreases replicative lifespan by 35% in the alpha strain [19030232]. Budding yeast
    YDR262W Deletion of YDR262W decreases replicative lifespan by 30% in the alpha strain [19030232]. Budding yeast
    INM2 INositol Monophosphatase 2 Deletion of INM2 decreases replicative lifespan by 70% in the alpha strain [19030232]. Budding yeast
    YGR071C Deletion of YGR071C decreases replicative lifespan by 60% in the alpha strain [19030232]. Budding yeast
    ANS1 Deletion of ANS1 decreases replicative lifespan by 25% in the alpha strain [19030232]. Budding yeast
    YKL069W Deletion of YKL069W increases sensitivity to oxidative stress and decreases replicative lifespan [19049972]. Budding yeast
    TDA5 Topoisomerase I Damage Affected 5 Deletion of TDA5 decreases replicative lifespan by 30% in the alpha strain [19030232]. Budding yeast
    DIF1 Damage-regulated Import Facilitator 1 Deletion of DIF1 decreases replicative lifespan by 20% in the alpha strain [19030232]. Budding yeast
    Factors are an extension of GenAge and GenDR.

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