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
    GHR growth hormone receptor Individuals with low GH/IGF-I signaling due to a defect in the growth hormone receptor (GHR) are protected against cancer. Among the human individuals with a defect in GHR no cancer deaths were observed. GHR deficiency does not appear to extend lifespan because it is associated with increased risk of heart disease [21325617]. Variants in GHR were found to be associated with longevity [19489743]. Human
    Lamp2a lysosomal-associated membrane protein 2 Lamp2a, the receptor for chaperone-mediate autophagy (CMA) decreases in abundance with age. Maintaining the amount of the Lamp2a (in a double transgenic mice) specifically in the liver at levels found in young adults prevents age-dependent decrease in receptor abundance at the cellular and organ levels. In this mice CMA activity is maintained until advanced ages which results in preservation of the autophagic activity and is associated with lower intracellular accumulation of damaged proteins, better ability to handle protein damage and improved organ function [19115216; 18690243]. Lamp2a expression restored not only CMA but also macrophagy and proteasomal degradation to the level observed in young liver as well as `youthful` mitochondrial function and cellular ATP abundance and overall youthful liver functions [18776878]. House mouse
    IL6 interleukin 6 (interferon, beta 2) Elevated IL-6 serum levels are associated with diseases, disability and mortality in the elderly. The proportion of homozyogtes for the G allele at -174 locus (a promoter genetic variability) decreases centenarian males, but not centenarians females. Only males, homozygous for the G allele at -174 locus have higher IL6- serum levels. Individuals who are genetically predisposed to produce high levels of IL-6 during aging (i.e. -174 locus GG homozygous men) are disadvantaged for longevity [11500818]. Human
    TSHR thyroid stimulating hormone receptor Two single nucleotide in the TSHR were associated with increased TSH in both centenarians and their offspring [19837933].TSHR was found to be associated with longevity [19837933]. TSHR was not found to be associated with longevity [19837933]. Human
    arf-3 ADP-Ribosylation Factor related 3 RNA interference of arf-3 does not affect lifespan of wild-type but suppresses lifespan extension by isp-1 mutation [22829775].
    dcp-66 Deacetylase Complex Protein 66 dcp-66 RNAi shortens the mean lifespan by 29% and suppresses lifespan extension by isp-1 mutation, but does not significantly affect lifespan extension neither by eat-2 nor daf-2 mutation [22829775]. Nematode
    CTA1 CaTalase A 1 CTA1 overexpression partially suppresses the shortened chronological lifespan by ISC1 mutation [21707788]. Budding yeast
    tps-2 Trehalose 6-Phosphate Synthase 2 RNA interference mediated inactivation of the trehalose-biosynthetic gene trehalose-6-phosphate synthase-2 (tps-2) decreases daf-2 mutant's long lifespan [20477758]. Nematode
    tps-1 Trehalose 6-Phosphate Synthase 1 RNA interference mediated inactivation of the trehalose-biosynthetic gene trehalose-6-phosphate synthase-1 (tps-1) decreases daf-2 mutant's long lifespan [20477758]. Nematode
    let-4 LEThal 4 let-4 (alias sym-5) is downregulated in space. RNA intereference of let-4 extends mean and 75%ile lifespan by 4%, but reduces maximum lifespan by 25% [22768380]. Nematode
    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
    Ucp3 uncoupling protein 3 (mitochondrial, proton carrier) Metabolic intensity (daily food energy/body mass) correlates with longevity in MF1 mice. The animals with the highest quartile of metabolic intensities have a mean lifespan of 36% longer than animals with the lowest quartile of metabolic intensities. The highest metabolism of long-lived animals can be attributed to increased uncoupling Ucp3 [15153176]. Skeletal muscle mitochondria isolated from high metabolism mice are more uncoupled that those from low metabolism mice [15153176]. House mouse
    UCHL1 ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) UCHL1 is assoicated with Parkinson's disease [9774100]. UCHL1 belongs to a family of de-ubiquitinating enzymes responsible for the hydrolysis of bonds between ubiquitin molecules and small adducts [11084366]. Decreased activity due to mutation may result in decreased labeling of abnormal proteins for clearance. Human
    SAG12 senescence-associated protein 12 Expression of SAG12 is specifically activated by developmentally controlled senescence pathways but not by stress- or hormone-controlled pathways [10579486; 10579487].
    RTG2 ReTroGrade regulation 2 RTG2 is required for replicative lifespan extension associated with the retrograde response, a pathway that signals the functional status of mitochondria to the nucleus to regulate the expression of several genes [11024000]. RTG2 is not required for replicative lifespan extension by DR [11024000]. RTG2 null mutants are not petite [8422683], but display various nutrient auxotrphies and alterations of carbohydrate metabolism [7727418]. Budding yeast
    PSEN1 presenilin 1 Mutations (more than 60 different) in PSEN1 are associated with Alzheimer's disease, of which all result in increased production of abnormally long amyloid beta-protein and an increase in senile plaque formation [10934557].PSEN1 was found to be associated with longevity [17903295]. Human
    PARK2 parkinson protein 2, E3 ubiquitin protein ligase (parkin) Parkin loss of function (e.g. due to deletion or point mutations) results in autosomal recessive juvenile parkinsonism, a form of Parkinson's disease with age of onset below 40 years. Associated phenotypes include resting tremor, rigidity, bradykinesia and postural instability is associated with selective neurodegeneration of the pigmented neurons in the brain stem (substiantia nigria and locus coereus) as well as the presence of intracytoplasmic inclusion bodies (Lewy bodies) [4735177].PARK2 was found to be associated with longevity [22279548]. Human
    sgg shaggy Several insertions of P-based vectors in the structural part of sgg are associated with alterations of male and female lifespan [22661237]. Fruit fly
    unc-51 UNCoordinated-51 unc-51(e369) mutation reduces mean but extends maximum lifespan. unc-51(e369) mutation reduces lifespan of eat-2(ad1116) mutants to that of wild-type [18219227]. Nematode
    NAC N-acetyl cysteine Treatment with 10 mM of NAC has no effect on the lifespan of wild-type, but fully abolishes the increased longevity of nuo-6 and severly limits that of isp-1. At high concentration (> 10-15 nM) NAC can be become deleteroius even on the wild-type [21151885]. Nematode
    Vitamin C Treatment with 1 mM vitamin C has no effect on lifespan of wild-type, but significantly shortens the lifespan of both isp-1 and muo-6 mutants [21151885]. Supplementation with vitamin C normalizes the median lifespan of wnr-1 and mir-124 mutants, which both exhibit premature aging [23075628]. Nematode
    PPG1 Protein Phosphatase involved in Glycogen accumulation 1 PPG1 deletion reduces significantly mean chronological lifespan under starvation/extreme DR [20657825]. Budding yeast
    FAR11 Factor ARrest 3 Deletion of FAR11 significantly reduces mean chronological lifespan under starvation/extreme DR relatively to wild-type [20657825]. Budding yeast
    FAR3 Factor ARrest 3 Deletion of FAR3 significantly reduces mean chronological lifespan under starvation/extreme DR relatively to wild-type [20657825]. Budding yeast
    HNRNPD eterogeneous nuclear ribonucleoprotein D (AU-rich element RNA binding protein 1, 37kDa) HNRNPD controls inflammation by turning off the inflammatory response to stop the onset of septic shock. Cessation of inflammatory cytokine respisne is mediated partly through cytokine mRNA degradation facilitated by RNA-binding proteins, including HNRNPD. HNRNPD deletion leads to accelerated aging as evidenced by strinking telomere erosion, markedly increased DNA damage repsosne at telomere ends, pronounced cellular senescence and rapid premature aging that increases with successive generations. HNRNPD which is a family of four related genes also maintains the integrity of chromosomes by activating telomerase, because HNRNPD strongly activates the transcription promoter for Tert [Pont et al., 2012]. House mouse
    Factors are an extension of GenAge and GenDR.

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