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
    Slc25a4 solute carrier family 25 (mitochondrial carrier, adenine nucleotide translocator), member 4 Knockouts exhibited a shortened lifespan and increased hydrogen peroxide production and in some tissues. House mouse
    Stub1 STIP1 homology and U-Box containing protein 1 Knock-out mice exhibited a deregulation of protein quality control accompanied by a short lifespan and accelerated age-related pathophysiological features. House mouse
    Terc telomerase RNA component Telomerase null mice exhibit age-dependent telomere shortening and shortened lifespan with succeeding generations. Median lifespan is reduced by 26% in G6 Terc(-/-) mice compared to wild-type or G1-G3 Terc(-/-) (18 months vs. 24 months). G6 Tec(-/-) display hair greying, hair loss, and ulcerative skin lesions, as well as impaired response to wound healing and hematoitopitic ablation, and an increased incidence of cancer [10089885]. Cells from Terc(-/-) mice (G4 and upward) exhibit chromosomes lacking detectable teloemre repeats, aneuplody, and end-to-end fusions [9335332]. House mouse
    Top3b Topoisomerase (DNA) III beta Homozygous disruption of Top3b results in a normal development but a shorter lifespan (by approximately 70%) accompanied by lesions in multiple organs in C57BL/6 [11331780]. Yeast Top3 physically interacts with Sgs1 [7969174]. Human TOP3A interacts with BLM [10734115; 10728666] and both TOP3A and TOP3B interact with RECQ5 [10710432]. House mouse
    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
    Trp63 Transformation related protein 63 Heterozygous Trp632 mutant mice have a shortened lifespan (by 21.5%) and display features of accelerated aging [16107615]. The decreased longevity in Trp63(+/-) mice is almost identical to that of Trp53(+/m) mice in which enhanced Trp53 activity provides resistance to spontaneous tumors while simultaneously accelerating aging [16107615]. Trp63(+/-) are not susceptible to spontaneous tumors [16107615]. House mouse
    Xrcc5 X-ray repair complementing defective repair in Chinese hamster cells 5 Deletion results in signs of premature ageing such as osteopenia, atrophic skin, hepatocellular degeneration, and age specific mortality. House mouse
    Xrcc6 X-ray repair complementing defective repair in Chinese hamster cells 6 XRCC5 and XRCC6 double knockout mice show decreased lifespan and signs of premature ageing without increase cancer incidence. House mouse
    XPA Xeroderma pigmentosum, complementation group A Mutant mice exhibit symptoms of premature ageing, including reduced lifespan, osteoporosis and kyphosis, osteosclerosis, early greying, cachexia, and infertility. House mouse
    Zmpste24 zinc metallopeptidase, STE24 homolog (S. cerevisiae) Knockout mice exhibit nuclear architecture abnormalities and signs of accelerated ageing. House mouse
    Factors are an extension of GenAge and GenDR.

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