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
    gsa-1 RNAi against R06A10.2 decreases mean and maximum lifespan by 83-85% and 48%, respectively [18059442]. Nematode
    ATM ataxia telangiectasia mutated Individuals with ataxia-telangiectasia (AT) have a decreased lifespan, with a maximum of 52 years [3864931].ATM was found to be associated with longevity [22960875].ATM was found to be associated with longevity [20816691]. ATM was found to be associated with longevity [22960875]. ATM was found to be associated with longevity [22960875]. Human
    rpt-1 proteasome Regulatory Particle, ATPase-like 1 rpt-1 RNAi in the adulthood decreases the mean and maximum lifespan by 28 and 50%, respectively [23144747]. Nematode
    pat-3 Paralysed Arrest at Two-fold 3 pat-3 RNAi in the adulthood decreases mean and maximum lifespan by 28% and 50%, respectively [23144747]. Nematode
    dpy-27 DumPY : shorter than wild-type 27 dpy-27 RNAi in the adulthood shortens mean and maximum lifespan by 24 and 25%, respectively [23144747]. Nematode
    snap-1 SNAP (Soluble NSF Attachment Protein) 1 snap-1 RNAi in the adulthood reduces mean and maximum lifespan by 34 and 50%, respectively [23144747]. Nematode
    pcf-11 cleavage and polyadenylation factor homolog 11 pcf-11 RNAi in the adulthood decreases mean and maximum lifespan by 19 and 25% [23144747]. Nematode
    lys-1 LYSozyme lys-1 RNAi in the adulthood extends the lifespan [New longevity regulators]. Overexpression of lys-1 increases mean and maximum lifespan by 5 and 26%, but has no significant effect on median lifespan [22737090]. Nematode
    sptf-3 Specificity Protein Transcription Factor 3 RNAi against sptf-3 decreases mean and maximum lifespan by 20 - 28% and 28%, respectively. sptf-3 RNAi in the adulthood decreases the mean and maximum lifespan by 23 and 37% [23144747]. sptf-3 overexpression extends lifespan [18059442]. Nematode
    rab-5 RAB family 5 rab-5 RNAi in the adulthood reduces mean and maximum lifespan by 38 and 50% [23144747]. Nematode
    rpn-11 proteasome Regulatory Particle, Non-ATPase-like 11 rpn-11 RNAi in the adulthood decreases mean and maximum lifespan by 19 and 25%, respectively [23144747]. Nematode
    cdtl-7 CDc-Two Like 7 RNAi against cdtl-7 starting in the adulthood decreases mean and maximum lifespan by 22 and 25%, respectively [23144747]. Nematode
    snap-29 SNAP (Soluble NSF Attachment Protein) homolog 29 RNAi against snap-29 starting in the adulthood decreases mean and maximum lifespan by 49 and 72%, respectively [23144747]. Nematode
    ERG3 ERGosterol biosynthesis Deletion of ERG3 decreases replicative lifespan under AL, cancels out replicative lifespan extension of 0.5% glucose DR and results under DR also into a shorter replicative lifespan than under AL [18690010]. Budding yeast
    ATG16 AuTophaGy related 16 Under AL atg16 mutation shortens chronological, but not replicative lifespan. 0.5% glucose DR extends chronological lifespan of atg16 mutants, but amino-acid DR does not extend the short chronological lifespan of atg16 mutants (similar to several other autophagy mutants). ADE4 deletion in atg16 mutants results only in a partial extension of chronological lifespan by 0.5% glucose DR. The long chronological lifespan of tor1 mutants requires ATG16 [20421943]. Budding yeast
    ubc-18 UBiquitin Conjugating enzyme 18 ubc-18 overexpression is unable to extend lifespan (possibly, UBC-18 is not limiting for WWP-1 function in lifespan). Loss of ubc-18 function by mutation or RNAi reduces lifespan at 25 degree Celsius, but only slightly at 20 degree Celsius. RNAi depletion of ubc-18 completely suppresses increased longevity of eat-2 mutants. RNAi depletion of ubc-18 has no effect on long lifespan of isp-1 or daf-2 mutants. Combined knockdown of wwp-1 and ubc-18 by RNAi does not shorten lifespan any further than RNAi of either single gene. Knockdown of ubc-18 suppresses extended lifespan of wwp-1 overexpression [19553937]. Nematode
    aqp-1 AQuaPorin or aquaglyceroporin related 1 aqp-1 expression changes in response to glucose or glycerol. Similar to daf-16 and hsf-1 mutants, aqp-1 mutants were short-lived, and their short lifespan was not further decreased by glucose. Overexpression of aqp-1::GFP rescues short lifespan of aqp-1 deletion mutants and partially prevented glucose from shortening lifespan. Glucose or glycerol feeding downregulates aqp-1 in wild-type. In daf-16 and/or hsf-1 mutants aqp-1 is repressed and glucose feeding does not significantly affect its expression. aqp-1 mutation does not further decrease the short lifespan of daf-16 and/or hsf-1 mutants. aqp-1 transgene is expressed in pharynx and intestine (which behaves as entire endoderm of animal, including adipose tissues). Dietary glucose does not cause significant differences in levels of glucose or glycerol in wild-type vs. aqp-1 mutants [19883616]. 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
    cbp-1 CBP/p300 homolog 1 bDR and daf-2 mutation induce cbp-1 expression. There is no decrease in cbp-1 expression in whole C. elegans during aging. Overexpression of cbp-1 does not significantly affect lifespan. daf-16 RNAi and cbp-1 RNAi reduce average lifespan under AL to about the same extent. Inhibiting cbp-1 via RNAi by 50%, specifically in adult phase and completely blocks lifespan extension of DD, bDR as well as eat-2, glp-1 and clk-1 mutation, but only partially that of daf-2 mutation and not at all that of cold. cbp-1 RNAi completely blocks the lifespan increase by daf-2 mutation under bDR. cbp-1 RNAi blocks the delay of other age-related pathologies by bDR. cbp-1 RNAi prevents protective effects of bDR and accelerates ABeta42-related pathology. bDR significantly delays onset of paralysis even in presence of cbp-1 RNAi. cbp-1 RNAi specifically in adults completely blocks lifespan extension by three distinct protocols of DR (mutation of eat-2), partly by daf-2 mutation but not of cold and blocks the delay of other age-related pathologies by bDR. cbp-1 RNAi has no effect on lifespan in daf-16 hypomorphic mutants. Combining cbp-1 and daf-16 RNAi in wild-type produces similar lifespan as either alone. Resistance to oxidative stress is strikingly reduced by cbp-1 RNAi and cbp-1 RNAi attenuates the protection against oxidative stress by bDR. cbp-1 RNAi accelerates accumulation of autofluorescence, but has no effect on activity, egg laying, or pharyngeal pumping. cbp-1 RNAi does not block induction of daf-16 or hsf-1 by bDR, but does block the induction of DAF-16 target gene, sod-3, and HSF-1 target gene, sip-1 by bDR. cbp-1 RNAi blocks induction of sod-3 expression by daf-2 RNAi. cbp-1 RNAi does not block the increased Nile Red staining produced by daf-2 mutation, but enhanced Nile Red staining. cbp-1 RNAi blocks the effect of bDR on metabolic gene expression from glycolysis towards beta-oxidation. Drugs that enhance histone acetylation increase lifespan and reduce ABeta42-related pathologies, but these protective effects are completely blocked by cbp-1 RNAi. cbp-1 RNAi decreases H4 Lys 5 acetylation and blocks the extension of lifespan as well as delays the onset of paralysis by ABeta1-42 transgene under AL and bDR by sodium butyrate (NaB) and trichostatin (TSA). cbp-1 RNAi does produce dye-filling defects in all C. elegans amphid neurons (ASI, ADL, ASK, AWB, ASH, and ASJ) [19924292]. Nematode
    dve-1 DVE (Defective proVEntriculus in Drosophila) homolog) 1 dve-1 RNAi attenuates lifespan extension by bDR, but only partially that of daf-2 mutation. dve-1 RNAi attenuates protection against oxidative stress by bDR. dve-1 expression is not induced by bDR [19924292]. Nematode
    phb-1 mitochondrial ProHiBitin complex 1 phb-1 RNAi shortens lifespan of wild-type, aak-2, cep-1 (p53) and jnk-1 mutants, but increases lifespan of daf-2, daf-7, daf-4, daf-11, gas-1, mev-1, isp-1, clk-1, nhr-49, fat-7 and gld-1 mutants. daf-16 mutation fully suppressed the exceptional long-lifespan of prohibitin-depleted (via RNAi) daf-2 mutants [19812672]. Nematode
    phb-2 mitochondrial ProHiBitin complex 2 phb-2 RNAi shortens lifespan of wild type, aak-2, cep-1 (p53) and jnk-1 mutants, but increases lifespan of daf-2, daf-7, daf-4, daf-11, gas-1, mev-1, isp-1, clk-1, nhr-49, fat-7, gld-1 mutants. daf-16 mutation fully suppressed exceptionally long-lifespan of via RNAi prohibitin-depleted, daf-2 mutants [19812672]. Nematode
    Thor Null mutation in Thor (alias d4E-BP) causes a significant decrease in longevity (-25% median lifespan in males). Thor is strongly upregulated during starvation. foxo and Thor null mutants are compromised in stress resistant. Stress resistance of foxo null mutants is rescued by Thor overexpression [16055649]. Thor is upregulated on the protein level in a foxo-independent manner upon DR, while it is transcriptional induced in a foxo-dependent fashion by starvation. Thor null mutants cancel out DR-induced lifespan extension, because mutants exhibit a diminished change in lifespan when nutrient conditions were varied. Ubiquitously expression of Thor rescued DR response in females and males. Thor null mutants have a wild-type similar reduction in egg production upon DR. Ubiquitously overexpression of wild-type Thor causes no change under AL, but an activated allele (with more than 3-fold increased binding activity to delF4E) significantly extends lifespan of females (weak allele) and females as well as males (strong allele). Mean lifespan is extended by 11 to 40%. Median lifespan of males and females is enhanced by by 11 and 22%, respectively. Maximum lifespan is extended by 16 and 18% for males and females, respectively. Under DR (0.25% YE) there is no lifespan extension, beyond the effect of DR alone, in all (wild-type, weak and strong) Thor alleles [19804760]. Lifespan of animals with increased Pten and 4E-BP activity in muscle exhibit and extended mean and maximum lifespan by 20% and 15.8% [21111239]. Fruit fly
    YOL092W Deletion of YOL092W decreases mean and maximum replicative lifespan by 36 and 21%, respectively. Lifespan of YOL092Y deletion mutants is extended by 0.5% glucose restriction [22912585]. Budding yeast
    Factors are an extension of GenAge and GenDR.

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