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

prometheus--2.jpg

  • symbol name observation species
    mir-277 Constitutive miR-277 expression shortens lifespan and synthetically lethal with reduced insulin signaling, indicating that metabolic control underlies this phenotype. Transgenic inhibition with a miRNA sponge construct also shortens lifespan [23669073]. miR-277 is downregulated during adult life [23669073]. mir-277 controls branched-chain amino acid catabolism and as a result it can modulate the activity of TOR kinase [23669073]. Fruit fly
    CG3776 Both overexpression and underexpression of CG3776 (alias Jhebp29) reduces the mean lifespan, where the reduction in males is slightly higher. The lifespan of male flies with under- and overexpressed CG3776 is reduced by 38.8 and 42.6%, respectively when compared with Oregon R flies.The lifespan of female flies with under- and overexpressed CG3776 is reduced by 31.6 and 35%, respectively when compared to Oregon R flies. Among the males and females, relatively to Oregon R and EP835/CyO, the age-specific survival of EP835/EP835 and EP835/Gal4 is reduced in both log-rank and Wilcoxon tests (P < 0.001); survival of EP835/EP835 and EP835/Gal4 differed using the log-rank-test (male: P<0.001; female: P=0.027) [18275960]. Fruit fly
    nlp-7 Neuropeptide-Like Protein nlp-7 RNAi or overexpression reduces oxidative stress resistance and shortens lifespan of wild-type under AL. nlp-7 RNAi significantly reduces extended lifespan of eat-2 mutants, but failed to block lifespan extension of age-1 or clk-1 mutants. Lifespan of nlp-7 mutants increases only moderately by sDR [19783783]. nlp-7 expression is induced under DR via the use of a chemically defined axenic medium [17023606] and by sDR [19783783]. Nematode
    cup-4 Coelomocyte UPtake defective 4 cup-4 RNAi or overexpession reduces oxidative stress resistance and shortens lifespan of wild-type under AL. cup-4 RNAi significantly reduces the extended lifespan of eat-2 mutants, but failed to block lifespan extension of age-1 or clk-1 mutants. Lifespan of cup-4 mutants increases only moderately by sDR [19783783]. Nematode
    GTS1 Glycine Threonine Serine repeat protein 1 Deletion or overexpression of GTS1 shortens replicative lifespan significantly and slightly, respectively (wt:26, Delta:16 and OE:24) [8573138]. 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
    Trp53 Transformation related protein 53 Mice heterozyogous for an allele of p53 that removes the 5' portion of the protein demonstrate decreased cancer, permature aging phenotypes, and shortened lifespan in the mixed inbred C57BL/6–129/Sv background. It has been proposed that the this allele of p53 results in increased activity/overexpression [11780111]. Decreased activity of Trp53 results in increased cancer and decreased apoptosis. Mutant mice with activated Trp53 display enhanced resistance to spontaneous tumours and signs of premature ageing including reduced lifespan, osteoporosis, organ atrophy and a diminished stress tolerance [11780111]. However, super-p53 mice generate by a transgenic copy of a large genomic segment containing an intact and complete copy of p53 have an ehanced response to DNA damage, are significantly protected from cancer and had no indication of accelerated aging [12426394]. super-Ink4a/Arf/p53 mice have a synergic protection against cancer and delayed aging [Workshop RoSyBa 2011]. House mouse
    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
    • 8 factors
    Factors are an extension of GenAge and GenDR.

    Comment on This Data Unit