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
    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
    nlp-7 Neuropeptide-Like Protein nlp-7 RNAi or overexpression reduces oxidative stress resistance and shortens lifespan of wild-type under AL. nlp-7 RNAi significantly reduces extended lifespan of eat-2 mutants, but failed to block lifespan extension of age-1 or clk-1 mutants. Lifespan of nlp-7 mutants increases only moderately by sDR [19783783]. nlp-7 expression is induced under DR via the use of a chemically defined axenic medium [17023606] and by sDR [19783783]. Nematode
    cup-4 Coelomocyte UPtake defective 4 cup-4 RNAi or overexpession reduces oxidative stress resistance and shortens lifespan of wild-type under AL. cup-4 RNAi significantly reduces the extended lifespan of eat-2 mutants, but failed to block lifespan extension of age-1 or clk-1 mutants. Lifespan of cup-4 mutants increases only moderately by sDR [19783783]. Nematode
    W09C5.8 RNAi against W09C5.8 increases mean and maximum lifespan by 62% and 50%, respectively [12447374]. Lifespan extension by RNAi of W09C5.8 is not suppressed by daf-16. Loss of W09C5.8 activity via RNAi can also result in a shortened lifespan, reduced fertility and defects in mitochondrial respiratory chain function [19074434]. W09C5.8 RNAi animals have lower ATP content and oxygen consumption [12447374]. Nematode
    old-1 Overexpression Longevity Determinant Overexpression of old-1 in transgenic animals increases mean and maximum lifespan by 40-100% (average 65%) and 97%, respectively. old-1 overexpression of increases stress resistance (to heat by 20% and ultraviolet irradiation by 33%) without altering development or fertility. Effects of old-1 on lifespan and stress resistance is under regulation of daf-16 [9768365]. old-1 mRNA levels are upregulated in response to stress and in daf-2 as well as age-1 mutant backgrounds [11591319]. old-1 expression is downregulated in daf-2 mutants [12845331]. old-1 RNAi in an rrf-3 mutant background slightly extends lifespan [12845331]. old-1 is expressed in the anterior region of the worm, in neuronal, hypodermal and pharyngeal tissues as well in the proximal region in the male gonad. Its expression is detectable in young adults and appears to increase as animals age and in response to heat, starvation, or UV irradiation. Nematode
    mdh-1 Malate DeHydrogenase RNAi against mdh-1 decreases median lifespan by 10% in wild type animals and by 16% in daf-2 mutants [18006689]. mdh-1 RNAi started after the animal reached the late L4 stage increases mean and maximum lifespan by 4-27% and 9% [22103665]. Nematode
    ins-1 INSulin related Increased dosage of ins-1 under its own promoter as well as a heat shock promoter increases lifespan by 25% and is also able to increase the lifespan of daf-2 mutants [11274053]. ins-1 RNAi increases lifespan by 20%. ins-1 is differentially transcribed in daf-16 and daf-2 animals [12845331]. Overexpression of ins-1 also causes an increase in dauer formation and can enhance the dauer formation of daf-2 mutants [11274053]. Nematode
    glp-1 abnormal Germ Line Proliferation glp-1(qu158) mutations result in defects in germ-line proliferation and extension of lifespan by about 30%, which requires daf-16 [11799246]. glp-1(bn18) mutation increases mean, median, 75th %ile and maximum lifespan by 27-37, 26-33, 24-29 and 35%, respectively [22560223]. glp-1(e2141) mutation increases mean (32%) and maximum (53%) lifespan [18828672]. Two alleles of glp-1 that cause overproliferation of gemrline cells, glp-1(oz112gf) and glp-1(q485), result in a shortened lifespan [11799246]. In glp-1 mutants, Z2 and Z3 generate only a few germ cells, which enter meiosis and differentiate as sperm [3677168]. Nematode
    eft-2 Elongation FacTor Post-developmental RNA interference reduces mean lifespan by 15% [17673661]. Knockdown of eft-2 started after the animal reached the late L4 stage increases mean lifespan by 6-27% and 8%, respectively [22103665]. Nematode
    • 9 factors
    Factors are an extension of GenAge and GenDR.

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