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
    BHB β-hydroxybutyrate β-hydroxybutyrate (βOHB), ketone body is produced during a prolonged low-caloric or ketonic diet. Low concentrations of βOHB helps protect cells from "oxidative stress". dietary restriction (DR) spurs βOHB production. βOHB is an endogenous and specific inhibitor of class I histone deacetylases (HDACs). Exogenous βOHB administration, fasting or DR increases global histone acetylation in mouse tissues. HDAC inhibition by βOHB is correlated with global changes in transcription, including oxidative stress factors Foxo3a and Mt2. Cells treated with βOHB have increased histone acetylation at Foxo3a and Mt2 promoters. Both Foxo3a and Mt2 are activated by selective depletion of HDAC1 and HDAC2. normally keeps a pair of genes, namely Foxo3a and Mt2 switched off [http://www.biocompare.com/Life-Science-News/126847-Gladstone-Scientists-Discover-Novel-Mechanism-By-Which-Calorie-Restriction-Influences-Longevity/; http://www.sciencemag.org/content/early/2012/12/05/science.1227166].
    zyg-11 ZYGote defective: embryonic lethal zyg-11 RNAi in the adulthood extends the lifespan [New longevity regulators]. Nematode
    ZWINT ZW10 interactor ZWINT was found to be associated with longevity [22279548]. Human
    ZNF331 zinc finger protein 331 ZNF331 was found to be associated with longevity [21782286]. Human
    ZC395.10 Zinc finger Transcription Factor family ZC395.10 RNAi in the adulthood extends the lifespan [New longevity regulators]. Nematode
    ZBTB20 zinc finger and BTB domain containing 20 ZBTB20 was found to be associated with longevity [22279548]. Human
    YPT7 Yeast Protein Two 7 YPT7 deletion decreases replicative lifespan by 15% in the alpha strain [18340043]. Deletion of YPT7 cancels out replicative lifespan extension of 0.5% glucose restriction and results under DR also into a shorter replicative lifespan than under AL [18690010]. Budding yeast
    YHC3 Yeast Homolog of human Cln3 YHC3 deletion decreases 10-20% shortened lifespan [16435200]. Budding yeast
    YGL235W YGL235W increases replicative lifespan by 20% in the alpha strain [19030232]. Budding yeast
    YDL180W YDL180W deletion impairs DR-mediated replicative lifespan extension, but does not change lifespan on AL significantly [22912585]. Budding yeast
    yata yata mutation shortens the maximum lifespan by 68% and results in progressive deterioration of the nervous tissues and aberrant accumulation of Sec23 [19209226]. Fruit fly
    Yaf2 YY1 associated factor 2 Yaf2 is transcriptional upregulated in the cerebral cortex at the age 28 months under different longevity conditions such as under dietary restriction (DR) as well as in feeding switch regimens that result in extended lifespan, like early age switch to DR as well as the reverse switch under the influence of the DR-mimetic α-lipoic acid (i.e. DR switched to ad libitum+ lipoic acid) [Shona et al. 2013]. Norway rat
    Y56A3A.9 Y56A3A.9 RNA interference extends lifespan. Nematode
    Y41E3.11 human FANCD2 (Fanconi's anemia defect) ortholog Y41E3.11 RNAi in the adulthood extends the lifespan [New longevity regulators]. Nematode
    xrn-1 XRN (mouse/S. cerevisiae) ribonuclease related xrn-1 RNAi in the adulthood extends the lifespan [New longevity regulators]. Nematode
    XRCC5 X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining) XRCC5 was found to be associated with longevity [22406557; 16518718]. Human
    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
    XRCC4 X-ray repair complementing defective repair in Chinese hamster cells 4 XRCC4 was found to be associated with longevity [16518718]. Human
    XRCC3 X-ray repair complementing defective repair in Chinese hamster cells 3 XRCC3 was found to be associated with longevity [16518718]. Human
    XRCC1 X-ray repair complementing defective repair in Chinese hamster cells 1 XRCC1 was found to be associated with longevity [16518718]. Human
    XKR6 XK, Kell blood group complex subunit-related family, member 6 XKR6 was found to be associated with longevity [22279548]. Human
    XDH xanthine dehydrogenase XDH was found to be associated with longevity [22406557; 22279548]. Human
    WWOX WW domain containing oxidoreductase WWOX was found to be associated with longevity [22279548]. WWOX was found to be associated with longevity [24244950]. Human
    Sirt1 sirtuin 1 (silent mating type information regulation 2, homolog) 1 (S. cerevisiae) Whole-body deletion of Sirt1 in the adulthood results in mice which are seemingly normal in every way. When mice were given low doses of resveratrol after Sirt1 was disabled, there were no discernible improvement in mitochondrial function or any parameter, while mice with normal Sirt1 function given reservatrol showed dramatic increases in energy, mitochondrial biogenesis and function, AMPK activation and increased NAD+ levels in skeletal muscle. When mice lacking Sirt1 were given low doses of reserveratrol, AMPK was unaffected. When doses were significantly increased in these mice, AMPK was activated in a SIRT1-indepent manner, but still no benefit to mitochondrial function resulted [22560220]. Sirt1 overexpression mimicks the effect on reservatrol on mitochondrial function, but failed to extend lifespan [22560220]. SIRT1 knock-out mouse embryonic fibroblasts (MEFs) have a significant greater replicative capacity in culture. p19ARF levels are significantly reduced in SIRT1 knock-out MEFs [16054100]. Sirt1-null mice do not exhibit lifespan extension upon Dietary Restriction [18335035]. Sirt1 is required for high-magnitude circadian transcription of several core clock genes. It deacetylates Per2, Arntl and histones of clock-controlled genes [18662546]. SIRT1 directly [21187328] and indirectly [20450879] prevents telomere shortening. House mouse
    WDR72 WD repeat domain 72 WDR72 was found to be associated with longevity [22279548]. Human
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    • 25 of 2668 factors
    Factors are an extension of GenAge and GenDR.

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