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
    mev-1 Abnormal MEthyl Viologen sensitivity Loss of function in mev-1 shortens lifespan to 66% of wild-type (i.e. by 34%) and accelerates accumulation of aging-associated biomarkers such as protein carboynls and fluorescent materials. mev-1 mutants are hypersensitive to raised oxygen concentrations and their lifespan decreases dramatically as oxygen concentrations increase [9716135]. Mutation of mev-1 results in paraquat sensitivity, slow grows, and low fecundity. mev-1 mutants have a 50% reduction in superoxide dismutase activt relatively to wild-type [2233820]. Nematode
    ain-1 ALG-1 INteracting protein 1 RNA interference of ain-1 decreases median lifespan by 10% in wild type animals, 20% in a daf-2 background and 44% in daf-2/daf-16 double mutants [18006689]. Nematode
    agmo-1 AlkylGlycerol MonoOxygenase 1 RNA interference of agmo-1 decreases median lifespan by 30% in wild type animals and 60% in daf-2 mutants [18006689]. Nematode
    aak-2 AMP-Activated Kinase 2 AAK-2 could be a sensor that couples energy levels and insulin-like signals to lifespan. aak-2(ok524) knockout mutants have a 12% and 18% shorter mean and maximum lifespan, respectively as well as faster age-dependent accumulation of a lipofuscin-like fluorescent pigment in the intestine [15574588]. sDR increases AMP:ATP ratio. aak-2 mutation suppresses lifespan extension and delay of the decline in locomotor activity resulting from sDR. A constitutive active mutation of aak-2 is sufficient to cause increase stress resistance as well as to significantly extend lifespan. Both increased stress resistance and extended lifespan is reverted in daf-16 knockdown by RNAi. sod-3 mRNA is increased by constitutive active form of aak-2 and decreased by aak-2 mutation. The increase in sod-3 mRNA is dependent on expression of DAF-16. Worm and human AMPK phosphorylate DAF-16 (greatly enhanced by presence of AMP) at least in six residues (T166, S202, S314, S321, T463 and S466) [17900900]. aak-2 mutation cancels out the lifespan extension effect of sDR and PD, regardless of the concentration of bacteria or peptones. bDR significantly extends lifespan of aak-2 mutants, but to lesser extent than that of wild-type. eat-2 mutation extends the lifespan of aak-2 mutants to the same extent than that of wild-type. Resveratrol does not increase lifespan of aak-2 mutants [19239417]. daf-2(m577);aak-2(ok524) double mutant has a lifespan that is indistinguishable from those of aak-2(ok524) single mutant. Transgenic animals with a higher aak-2 gene dose live on average 13% longer with a maximum lifespan extension on up to 25% [15574588]. Nematode
    aakb-1 AMP-Activated Kinase Beta subunit 1 RNA interference of aakb-1 results in decreased lifespan and earlier accumulation of lipofuscin [16673436]. Nematode
    aakb-2 AMP-Activated Kinase Beta subunit 2 RNA interference of aakb-2 results in decreased lifespan and earlier accumulation of lipofuscin [16673436]. 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
    arl-8 ARF-Like 8 RNA interference of arl-8 decreases median lifespan by 35% in a daf-2 background and 9% in daf-2/daf-16 double mutants [18006689]. Nematode
    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
    alg-2 Argonaute (plant)-Like Gene 2 RNA interference of alg-2 decreases median lifespan by 24% in wild type animals and 50% in a daf-2 background [18006689]. Nematode
    arx-4 ARp2/3 compleX component 4 RNA interference of arx-4 decreases median lifespan by 61% in a daf-2 background and 51% in daf-2/daf-16 double mutants [18006689]. Nematode
    atp-3 ATP synthase subunit RNA interference against atp-3 results in lifespan extension [16103914]. atp-3 RNAi increases lifespan by 46% (mean by 33 and maximum by 70%). RNAi of atp-3 during larval stage is necessary and sufficient for lifespan prologation, while atp-3 RNAi only during the adulthood fails the extend lifespan. atp-3 RNAi results in reduced pharageal pumping, defection and motility as well as ATP levels and body size [12471266]. Nematode
    bus-8 Bacterially Un-Swollen (M. nematophilum resistant) 8 RNA interference of tag-249 decreases median lifespan by 58% in wild-type animals, 81% in a daf-2 background and 45% in daf-2/daf-16 double mutants [18006689]. Nematode
    bec-1 BEClin (human autophagy) homolog 1 bec-1 is required for normal dauer morphogenesis and lifespan extension. Knockdown of bec-1 via RNA interference results in a shortened mean and maximum lifespan by 14 and 5% [12958363]. bec-1 RNAi does not significantly change the lifespan of wild-type, but completely suppresses the longevity phenotype of eat-2 mutation [17912023; 18282106] and prevents lifespan extension by daf-2(e1370) mutation [12958363]. bec-1 RNAi causes the formation of abnormal dauers in a daf-2(e1379) background [12958363]. Nematode
    bar-1 beta-catenin BAR-1 may play a role in regulating daf-16 during dauer formation, particularly in conditions of oxidative stress as it directly interaction with DAF-16 and loss of bar-1 reduces activity of DAF-16 in dauer formation and lifespan. Deletion of bar-1 reduces mean (44%) and maximal (18%) lifespan, which is to a similar degree as seen to daf-16 mutants [15905404]. SMK-1 is important DAF-16 modulation of lifespan and specific stress response [5]. Nematode
    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
    blmp-1 Blimp1 (B Lymphocyte-induced Maturation Protein-1) homolog 1 RNA interference of blmp-1 decreases median lifespan by 17% in a daf-2 background and 20% in daf-2/daf-16 double mutants [18006689]. Nematode
    bra-1 BMP receptor Associated protein family bra-1(nk1) mutation reduces mean lifespan by 6-25% [17900898]. Nematode
    cst-1 Caenorhabditis STE20-like kinase 1 Knockdown of cst-1 shortens lifespan and accelerates tissue aging while its overexpression extends lifespan and delays aging in a daf-16-dependent manner [16751106]. Nematode
    calu-1 CALUmenin (calcium-binding protein) homolog RNA interference of calu-1 decreases median lifespan by 23% in a daf-2 background and 15% in daf-2/daf-16 double mutants [18006689]. 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
    ccr-4 CCR (yeast CCR4/NOT complex component) homolog 4 RNA interference of ccr-4 decreases median lifespan by 33% in wild type animals, 37% in a daf-2 background and 44% in daf-2/daf-16 double mutants [18006689]. 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
    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
    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
    Factors are an extension of GenAge and GenDR.

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