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
    Dcr-2 Dicer-2 Median lifespan of homozyogous and transheterozyogous Dcr-2 mutants is reduced by 18-36% in males and by 27-36% in females. Dcr-2 loss changes the expression of mostly metabolic genes implicated in stress resistance and aging. Dcr-2 mutants are hypersensitive to oxidative, endoplasmic reticulum, starvation and cold stress as well as abnormal lipid and carbohydrate metabolism [21889502]. Fruit fly
    alg-1 Argonaute (plant)-Like Gene Adult-specific knockdown of the C. elegans argonaute-like gene 1 alg-1 results in shortened lifespan with a reduction in the mean and maximum lifespan by 9 - 16% and 14%, respectively [21810936]. Nematode
    AVT1 Amino acid Vacuolar Transport 1 Overexpressing or deleting AVT1 is sufficient to extend or shorten replicative lifespan, respectively [23172144]. Overexpression of AVT1 prevents mitochondrial dysfunction, prevents alterations in mitochondrial structure and ΔΨ of aged cells even through the vacuolar acidity is reduced in these cells. AVT1 overexpression extends the mean, median and maximum replicative lifespan by 28, 28, and 22%, respectively [23172144]. Deletion of AVT1 accelerates the development of age-induced mitochondrial dysfunction without effecting the kinetics of vacuolar acidity decline and prevents the suppression of mitochondrial dysfunction by VMA1 and VPH2 overexpression without affecting vacuolar acidity. AVT1 deletion decreases mean, median and maximum replicative lifespan by 21, 22, and 12%, respectively [23172144]. Budding yeast
    pash-1 PArtner of DroSHa (DRSH-1 interactor) Inactivation of DGCR8/pash-1 in nematode reduces lifespan apparently due to accelerated aging. This intervention abrogates (lin-14 mutation and jnk-1(OE)) and suppresses (eat-2 and glp-1 mutants) several lifespan extending interventions, but not that conferred insulin-like signalling inhibition (daf-2 mutant) [23097426]. pash-1 mutants have a decreased lifespan and display phenotypic and molecular signs of advantaged age earlier. pash-1(mj100) temperature sensitive loss-of-function mutation decreases (at the permissive temperature) mean and maximum lifespan by 31 and 71%, respectively. At the restrictive temperature pash-1 mutants are slightly short-lived with a mean and maximum lifespan reduction by 13 and 54%. Lifespan of pash-1 mutants is reduced by a 24h upshift to 25 degree Celsius at the young adult stage with (36 and 78% reduction mean and maximum lifespan, respectively) [23097426]. The rescue of pash-1 expression all tissues restored almost normal lifespan. Rescue specifically in hypodermis, pharynx muscle, gut had no effect on lifespan. Rescue in body wall muscle marginal extended the lifespan, while rescue specifically in the neurons significantly restored mean but not maximum lifespan. Lifespan was also restored by combined rescue in hypodermis and muscle [23097426]. Nematode
    OSH2 OxySterol binding protein Homolog 2 Deletion of OSH2 decreases mean chronological lifespan [20657825]. Budding yeast
    VAC14 VACuole morphology and inheritance mutant 14 VAC14 mutants have a single vacuole and shortened lifespan on normal media [16293764]. Budding yeast
    gei-4 GEX Interacting protein 4 gei-4 RNAi in the adulthood reduces mean and maximum lifespan by 27 and 38% [23144747]. Nematode
    Hsp22 Heat shock protein 22 Overexpression of mitochondrial Hsp22 in all cells or specifically in motorneurons (using GAL4/UAS binary system) increases life lifespan by 32% and resistance to oxidative stress [19948727; 20036725]. Ubiquitous or a targeted expression of Hsp22 within motorneurons increases the mean lifespan by more than 30%. Hsp22 shows beneficial effects on early-aging events since the premortality phase displays the same increase as the mean lifespan [14734639]. Animals that do not express Hsp22 (due to a transposition into its transcriptional starting site) have a 40% decrease in lifespan, exhibit a 30% decrease in locomotor activity and are sensitive to mild stress [20036725]. Doxycyline-regulated overexpression of Hsp22 makes animals more sensitive to heat and oxidative stress as well as reduces the mean lifespan by up to 21%, particularly at higher culture temperature [15491684]. Hsp22-promoter driven reporter overexpression reduces mean and maximum lifespan [19420297]. Histone deacetylase inhibitor Trichostatin A (TSA) extends the lifespan of *Drosophila melanogaster* by promoting the hsp22 gene transcription, and affecting the chromatin morphology at the locus of hsp22 gene along the polytene chromosome [15346199]. Fruit fly
    phi-50 RNA interference of phi-50 decreases mean lifespan by 29% and suppresses lifespan extension by isp-1 and eat-2 mutation but does not significantly affect lifespan extension by daf-2 [22829775]. Nematode
    nekl-2 NEK (NEver in mitosis Kinase) Like 2 RNA intereference of nekl-2 decreases lifespan by 24% and suppresses lifespan extension by eat-2 mutation [22829775]. Nematode
    wnk-1 mammalian WNK-type protein kinase homolog 1 RNA interference of wnk-1 decreases lifespan by 9% and suppresses lifespan extension by eat-2 mutation [22829775]. Nematode
    cpf-2 Cleavage and Polyadenylation Factor 2 RNA interference of cpf-2 decreases mean lifespan by 6% and suppresses lifespan extension by eat-2 mutation [22829775]. Nematode
    pas-3 Proteasome Alpha Subunit 3 RNA interference of pas-3 shortens mean lifespan by 7% and suppresses lifespan extension by isp-1 mutation [22829775]. Nematode
    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
    pck-1 Phosphoenolpyruvate CarboxyKinase 1 RNA interference of pck-1 during the adulthood significantly shortens lifespan of both wild-type and eat-2 mutants. RNAi knockdown of pck-1 from hatching cases larval lethality. Overexpression of pck-1 greatly increases content of PEPCK-C, markedly induces enzyme activity and significantly increases mean, 75%ile, and maximum lifespan by 19-23%, 17-22%, and 21% [22810224]. Nematode
    pyk-1 PYruvate Kinase 1 RNA interference of pyk-1 during adulthood significantly shortens the lifespan of both wild-type and eat-2 mutants. RNAi knockdown of pyk-1 from hatching causes larval lethality. PYK-1 is downregulated in eat-2 mutants [22810224]. pyk-1(ok1754) mutation extends the lifespan and this effect is non-additive with the lifespan extension mediated by DDS treatment [20974969]. Nematode
    enol-1 ENOLase 1 RNA interference of enol-1 during adulthood significantly shortens the lifespan of both wild-type and eat-2 mutants. RNAi knockdown of enol-1 from hatching causes larval lethality. ENOL-1 downregulated in eat-2 mutants [22810224]. Nematode
    TEC1 Transposon Enhancement Control 1 Tec1 is a positive regulator of chronological lifespan. Absence of TEC1 causes a significant shortened chronological lifespan, but does not block chronological lifespan extension by rapamycin. TEC(AxY) mutation also reduces chronological lifespan, although not so pronounced as strains lacking TEC1. Rapamycin-induced chronological lifespan extension is almost completely blocked by TEC(AxY) allele [21840851]. Budding yeast
    NTH2 Neutral TreHalase 2 Deletion of NTH2 shortens mean chronological lifespan by 39% (at 30 degree Celsus in BY4742) [22783207]. NTH2 mutant cells have elevated trehalose concentration before they enter the non-proliferative stationary growth phase which remained high during the stationary phase. NTH2 deletion cells have no altered ROS levels in pre-quiescent cells [22783207]. Budding yeast
    TPS1 Trehalose-6-Phosphate Synthase 1 Deletion of TPS1 decreases intracellular trehalose concentration and shortens the mean chronological lifespan by 74% (at 30 degree Celsus in BY4742) [22783207]. Budding yeast
    ESA1 esa1-531 mutant has an even shorter chronological lifespan than PKA1 deletion mutant in both 2% glucose (ad libitum) and water (extreme DR) at 30 degree Celsius, a semipermissive temperature. At the permissive temperature (25 degree Celsius) there is little difference [19303850]. Budding yeast
    Lep leptin Lep knockout results in ob/ob mice which eats excessively and becomes profoundly obese. ob/ob mice live shorter on ad libitum, but achieve a lifespan similiar to control levels under DR, yet their precentage of body fat is much greater that that of controls [6608731]. House mouse
    ACH1 Acetyl CoA Hydrolase 1 ACH1 deletion cells accumulate a high amount of extracellular acetic acid and display a reduced mean and maximum chronological lifespan. Maximum lifespan is reduced by 32%. Lifespan shortening is completely abrogated by alleviating the acid stress either by a DR regimen that prevents acetic acid production or by transferring chronologically aging mutant cells to water. Deletion of ACH1 is accompanied by reactive oxygen species accumulation, severe mitochondrial damage, and an early insurgence of apoptosis [22754872]. 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
    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
    Factors are an extension of GenAge and GenDR.

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