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
    Gr63a Gustatory receptor 63a Gr63a loss-of-function in female flies leads to 30% extended mean lifespan, increased fat deposition, and enhanced resistance to some (but not all) environmental stresses. Lifespan of males is not extended [20422037]. Overexpression of Gr63a has modest negative effect on lifespan [20422037]. Fruit fly
    mir-239 Mutating mir-239 increases mean and maximum lifespan by 12 and 36%, respectively, whereas overexpressing mir-239 decreases mean and maximum lifespan by 13 and 17 - 33%, respectively [21129974]. Nematode
    tdp-1 TAR DNA-binding Protein homolog 1 tdp-1(ok803) mutation increases mean and maximum lifespan at 20 degree Celsius but not at 25 degree Celsius. tdp-1(ok803) reduce the lifespan of daf-2(e1370) mutants, but does not does not reduces the lifespan of daf-16(mu86) mutants. RNAi against tdp-1 reduces lifepsna of daf-2(e1370) mutants. tdp-1 overexpression strains have a reduced lifespan at 20 and 25 degree Celsius [Vaccaro et al. 2012]. Nematode
    SAG101 senescence-associated protein 101 Antisense RNA interference of SAG101 in transgenic plants delays the onset of leaf senescence for approximately 4 days, whereas chemical induced overexpression of SAG101 causes precocious senescence in both attached and detached leaves of transgenic plants [11971136].
    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
    SCP1 S. cerevisiae CalPonin 1 Increasing actin dynamics by deletion of SCP1, encoding an actin bundling protein, increases replicative lifespan by 67% as well as chronological lifespan by 88%, whereas its overexpression leads to elevuated ROS levels and reduces chronological lifespan (in KAY446 strain) [15024029]. SCP1 is related to mammalian SM22/transgelin which is induced during senescence [9570922]. Budding yeast
    AFG3 ATPase Family Gene 3 Deletion of the mitochondrial AAA protease AFG3 increases replicative lifespan by 20% in the alpha and a strains [18340043], but decreases chronological lifespan by 37 - 51% in diploid cells [21447998]. AFG3 deletion changes mean, median and maximum lifespan by 15 to 26% 17 to 30% and -25 to +58%, respectively. AFG3 deletion leads to reduced cytoplasmic mRNA translation and its lifespan extension is independent of Sir2 and Hac1, but requires Gcn4. AFG3 deletion further extends the lifespan of cell deficient in both SIR2 and FOB1, but fails to extend the lifespan of dietary restricted cells or cells lacking GCN4. Gcn4 protein levels are increased in afg3 mutants. The deletion of AFG3 fails to extend the replicative lifespan in the W303AR strain. AFG3 deletion does deletion extend the replicative lifespan at 15°C. Budding yeast
    SNF1 Sucrose NonFermenting 1 Forced overexpression (high-copy 2 micro expression) of SNF1 shortens replicative lifespan to 75% of wild-type and is accompanied by signs of premature ageing, including progressive sterility, enlargement and fragmentation of the nucleus, redistribution of Sir3 to the nucleus, and more rapid accumulation of extrachromosomal rDNA circles [10921902]. SNF1 overexpression also reduced chronological lifespan [19164565]. Deletion of SNF1 increases replicative lifespan by 50% in the alpha strain [19030232], but decreases chronological lifespan [21076178]. Budding yeast
    S6k RPS6-p70-protein kinase Ubiquitous overexpression of a dominant-negative form of S6k (alias dS6K) increases mean lifespan by 22% and overexpression of a constitutively active form of S6k decreases mean lifespan by 34% at 29°C. Overexpression of a dominant-negative form of S6k protects mutants from deleterious effects of rich food, as if mimicking the effect of DR [15186745]. Fruit fly
    lin-14 abnormal cell LINeage 14 A loss-of-function mutation in lin-14 extends lifespan by 31% while a gain-of-function mutation decreases lifespan. The life-extending effects is dependent on daf-16 and hsf-1. Also, lin-14 is a target of lin-4 [16373574]. lin-14(n719) mutation extends mean and maximum lifespan of control animals by 20 and 67%, respectively [23097426]. Knockdown of lin-14 only during adulthood is sufficient to extend lifespan and suppresses the short lifespan phenotype of lin-4 mutants. Nematode
    • 10 factors
    Factors are an extension of GenAge and GenDR.

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