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
    EXO1 exonuclease 1 The rs1776180 C allele in the promoter of EXO1 is significantly enriched in female Germans centenarians and this can be replicated in 445 female French centenarians. The C allele leads to the loss of binding site for the basic helix-loop-helix transcription factor E47, resulting in higher EXO1 expression [19698732].EXO1 was found to be associated with longevity [19698732]. EXO1 was not found to be associated with longevity [23770741]. Human
    MAPK1 mitogen-activated protein kinase 1 Overexpression of human MAPK1 (alias ERK2) confers resistance to heat shock and oxidative stress extends median chronological lifespan by 24% and was statistically non-addative with cyr1-1 mutation [17662940].MAPK1 was not found to be associated with longevity [23020224]. MAPK1 was found to be associated with longevity [23020224]. Human
    BNA6 Biosynthesis of Nicotinic Acid 6 Deletion of BNA6 (alias QPT1) has no effect on replicative lifespan and is not required for lifespan extension by DR, but is lethal with mutation of NPT1 [11000115]. Deletion of BNA6 decreases chronological lifespan [17110466]. Nematode
    INS insulin Expression of human insulin under an inducible heat shock promoter increases nematode lifespan by 25% and is also able to enhance the lifespan of daf-2 mutants [11274053]. INS was found to be associated with longevity [22406557; 19367319; 17989723; 19489743]. Human
    TERT telomerase reverse transcriptase Telomerase-expressing cells (human foreskin fibroblasts, retinal pigment epithelial cells) maintain normal length of telomeres and continue to divide vigorously [9454332]. Cells expression telomerase have reduced staining for beta-galactosidase (a biomarker of cellular senescence) [9501072]. TERT expression is also able to prevent the accelerated replicative senescence observed in cells taken from Werner's patients [10615119]. A haplotype of TERT was correlated with both longer both longer telomere length and exceptional longevity. Mutations in TERT were overpresented in Ashkenazi centenarians [19915151].TERT was not found to be associated with longevity [22136229]. TERT was found to be associated with longevity [23562826]. Human
    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
    ctl-1 CaTaLase 1 ctl-1 loss of function shortens lifespan to 77% of wild-type animals. ctl-1 mutants accumulate fluorescent material faster than wild-type, indicating accelerated aging [12610632]. ctl-1 mutation prevents lifespan extension by daf-2 or clk-1. Mutation of ctl-1 reudces catalase activty by 50% [10335847]. All these results have been retracted. Nematode
    OSH7 OxySterol binding protein Homolog 7 Overexpression of OSH7 extends mean replicative lifespan. PERG6-OSH7 does not extend the maximum lifespan significantly [Xia et al., unpublished]. Deletion of the CC domain of Osh7 (Perg6-OSH7-ORD) greatly shortens the lifespan. Deletion of the Osh7's CC domain decreases lifespan (Perg6-OSH7-ORD) shortens the lifespan [Tang et al., personal communication]. Osh7 interacts with the late endosome ATPase Vps4 by their C-terminal coiled-coil (CC) domain. Budding yeast
    SNCA synuclein, alpha (non A4 component of amyloid precursor) Transgenic lines overexpressing either human wild-type or mutant (A53T) forms of the SNCA (alpha-synclein) gene under a pan-neuronal promoter live on average about 25% longer, even in weak (m577) and strong (e1370) daf-2 mutant backgrounds, and exhibited decreased pharyngeal pumping and egg-laying. Wild-type SNCA crossed into eat-2(ad1113) does not significantly effect lifespan compared to that of the background strain. Pumping rate in wild-type SCNA and A53T SCNA overexpression mutants were less than control already at day 1 of adulthood. The attenuation of lifespan exptesion by SNCA overexpression by growing on thick bacterial lawns, suggests that DR may explain some fo the effects on lifespan. SCNA overexpression increases average lifespan by 21.3% (wild-type) and 16.3% (A53T) [16782295]. Mutation of SCNA (alias alpha synclein) is associated with Parkinson's disease [9197268], which is characterized with resting tremor, rigidity bradykinesia and posural instability that are associated with selective neurodegeneration of the pigmented neurons in the brain stem (substantia nigra and locus coerues) and the presence of intracytoplasmic inclusion bodies (Lewy bodies) [Yamamura et al. 1973]. The mutated protein (Ala53Thr or Ala30Pro) may misfold, aggregate and resist degradation [11433374].SNCA was found to be associated with longevity [22912757]. SNCA was not found to be associated with longevity [22912757]. Human
    CAT catalase Overexpression of human catalase targeted to mitochondria (MCAT) extends mean and maximum lifespan by about 20% in mice. Inactivation of aconitase in heat mitochondria and mitochondrial damage is also reduced in long-lived CAT mutant mice [15879174]. The MCAT strain has a reduced severity of age-dependent arteriosclerosis and increased genomic stability, as indicated by an decrease in oxidative stress and mitochondrial deletions in heart and muscle tissues. Median and maximum lifespan in increased about 17 - 21% [16144468].CAT was not found to be associated with longevity [15472150]. Human
    • 10 factors
    Factors are an extension of GenAge and GenDR.

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