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
    pex16 peroxin 16 pex16 mutation lead to a reduced mean lifespan of one-third in females and on-fourth in males. The short lifespan can be rescued by the simultaneous overexpression of pex16 in the fat body and differentiated neurons [21826223]. Mutant flies lack normal peroxisomes, have an reduced adult body size (70%-85% smaller than controls) and rozy eyes, show locomotion defects in the development of the nervous system [21826223]. Fruit fly
    Prx5 Peroxiredoxin 5 Prx5 overexpression causes an increase in mean and median lifespan under normal conditions. It also leads to a small increase in maximum lifespan. dprx5(-/-) null mutants are comparatively more susceptible to oxidative stress, have higher incidence of apoptosis, and a shortened mean lifespan, but thee is no significant difference in maximum lifespan (10% survival) [21826223]. Fruit fly
    Pi3K92E Phosphatidylinositol-3-kinase Heterozyogous mutation in Pi3K92E fails to extend lifespan [11292874] and it is recessive lethal. Overexpression of a dominant-negative Pi3K92E (DP110) results in mutants that have impaired regeneration of the intestinal epithelium and are short lived with a reduction of the mean lifespan by 2.8% for males and 5.0% for females [20976250]. Fruit fly
    rho-7 rhomboid-7 rho-7 knockout flies have severe neurological defects and a much reduced lifespan [16713954]. Fruit fly
    Rbp9 RNA-binding protein 9 Rbp9 mutation significantly decreases longevity with a 33% reduction in median lifespan of males [20589912]. Fruit fly
    rb ruby Loss-of-function mutation reduces mean lifespan by 33% and maximum lifespan by 22% [17435236]. Fruit fly
    Sh Shaker Genetic mutation in Sh decreases lifespan by accelerating the aging process. At 25 degree mean and maximum lifespan is reduced by 16 and 22%, while by 18 degree Celsius the reduction is 32 and 21% [8582611]. Fruit fly
    SNF4Agamma SNF4/AMP-activated protein kinase gamma subunit Deletion of SNF4Agamma from the first day of the imaginal stage shortens mean lifespan by 23% and causes morphological and behavioural features of premature aging [18219227]. Fruit fly
    Sod2 Superoxide dismutase 2 (Mn) RNA interference of Sod2 results in increased oxidative stress and early-onset mortality in young adults [12456885]. Overexpression of Sod2 by 5-115% decreases lifespan by 4-5% without any compensatory changes in metablic rate, level of physical activity, or the levels of other antioxidants (Sod, Cat, and glutathione) [10545213]. Targeted overexpression of Sod2 in motor neurons alone extends lifespan by 30% [11113599]. Induced overexpression of Sod2 in adult animals extends lifespan up to 37% [12072463]. Overexpression of catalase in combination with SOD2 has no added benefit for lifespan [12072463]. Animals overexpressing SOD2 or catalase do not exhibit a decrease in metabolism as measured by oxgen consumption [12072463]. Sod2 overexpression results in a 20% increase in mean and maximum lifespan [18067683]. Fruit fly
    tert telomerase reverse transcriptase First-generation tert(-/-) zebrafish die prematurely with shorter telomeres. tert(-/-) fish develop degenerative phenotypes, including premature infertility, gastrointestinal atrophy, and sarcopenia. tert(-/-) mutants have impaired cell proliferation, accumulation of DNA damage markers, and a p53 response leading to early apoptosis, followed by accumulation of senescence cells. Apoptosis is primarily observed in the proliferative niche and germ cells. Cell proliferation, but not apoptosis, is rescued in tp53(-/-)tert(-/-) mutants, underscoring p53 as mediator of telomerase deficiency and consequent telomere instability [http://denigma.de/url/3p]. Zebrafish
    Trx-2 thioredoxin-2 Trx-2 mutants have a 25% reduction in maximum lifespan and exhibit lower tolerance to oxidative stress while animals carrying multiple copies of Trx-2 exhibit higher tolerance [17567437]. Fruit fly
    GCN4 Transcriptional activator of amino acid biosynthetic genes in response to amino acid starvation; expression is tightly regulated at both the transcriptional and translational levels Deletion of GCN4 increases the replicative lifespan by 10% in the alpha strain [19030232]. GCN4 deletion decreases the lifespan in the alpha and a strain [20657825]. The chronological lifespan of GCN4 deletion is strongly decreased in the a strain [20421943]. Budding yeast
    WRN Werner syndrome, RecQ helicase-like Mutation in WRN causes Werner Syndrome which characteristics includes prematurely aged facies, scleroderma-like skin changes, cataracts, arteriosclerosis, subcutaneous calcification, and diabetes mellitus [McKusick et al. 1963; 5327241]. Inheritance is autosomal recessive and malignancy is frequent. THe frequency is 3 per million individuals in Japan [7460386]. Cells from a Werner heterozygote exit the cell cycle at a faster rate than do normal cells [8265666]. Loss of WRN promoter aberrant mitotic recombination [11316787]. The single nucleotide polymorphism rs1800392 in WRN has been associated with exceptional longevity in a plethora of genetic signatures [22279548]. WRN was found to be associated with longevity [10069711; 20855428; 20855428; 20855428 ;17903295; 22406557; 16405962; 16405962; 16405962; 20855428; 20855428; 20855428; 22279548]. WRN was found to be associated with longevity [24244950]. Human
    Factors are an extension of GenAge and GenDR.

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