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
    mir-124 Loss of mir-124 increases reactive oxygen species formation and accumulation of the aging marker lipofuscin, reduces whole body ATP levels and results in reduction in lifespan [23075628]. Supplementation of vitamin C normalizes the reduced median lifespan of mir-124 mutants [23075628]. The expression of the conserved mir-124 in whole wrn-1 mutants (which premature age) is significantly reduced [23075628]. 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
    mir-58 mir-58(n4640) mutation decreases the mean lifespan by 20% [22482727]. Nematode
    mir-238 Mutating mir-238 decreases mean and maximum lifespan by 18 and 24% [21129974]. mir-238(n4112) mutation decreases mean lifespan by 20% [22482727]. Nematode
    mir-246 Mutating mir-246 decreases mean and maximum lifespan by 12%, while its overexpression increases mean and maximum lifespan by 6 and 5 - 14%, respectively [21129974]. Nematode
    unc-10 UNCoordinated Mutation in unc-10 reduces maximum lifespan 35% [17592521]. Nematode
    daf-16 Abnormal DAuer Formation DAF-16, fork head-related transcription factor (daf-16) Mutations in daf-16 suppresses life-extension caused by mutations in daf-2 [8247153]. daf-16 is required for lifespan extension by mutation of daf-2 or age-1 [8247153]. RNAi against daf-16 decreases lifespan of wild-type, daf-2 or glp-1 mutants [22509016; 16530050]. Loss of function alleles of daf-16 shorten lifespan, but some alleles have lifespan equal to wild-type [8247153]. daf-16 mutation significantly reduces lifespan under AL (-20%), but does not prevent lifespan extension by sDR. In another experiment daf-16 mutation totally suppresses lifespan extension by sDR [16720740]. sDR does not stimulate DAF-16 translocation to the nucleus, but daf-16 mutation cancels out the ability of sDR to extend lifespan and to delay the decline in locomotor activity [17900900]. DR by bacterial dilution extends lifespan of daf-16 mutants [17538612]. daf-16 mutation decreases lifespan under AL, but fails to prevent bDR to further extend lifespan [18331616]. IF-induced lifespan-extension by either 24h/48h/72h per 4 days is significantly diminished in null mutants of daf-16. All these regimens extend lifespan of daf-16 to a lesser extent than that of wild-type. daf-16 partially mediates IF-induced longevity [19079239]. Glucose or glycerol does not shorten lifespan of daf-16 mutants [19883616]. daf-16 mutation cancels out the lifespan extension effect of sDR and PD, regardless of the concentration of bacteria or peptones. bDR significantly extends lifespan of daf-16 mutants, but to a lesser extent than that of wild-type. eat-2 mutation extends the lifespan of daf-16 mutants to the same extent than that of wild-type. Resveratrol extends lifespan of daf-16 mutants [19239417]. daf-16 RNAi completely blocks the lifespan extension by daf-2 mutation, but only partially by bDR. daf-16 RNAi attenuates protection against oxidative stress by bDR. daf-16 expression is induced by bDR [19924292]. Knockdown of daf-16 decreases mean and maximum lifespan by 50% and 54%, respectively [22509016]. DAF-16 reduces expression of rsks-1 and daf-15 [15253933; 22560223]. daf-16(mgDf47) decreases mean (18-37%) and maximum (29%) lifespan [18828672]. Overexpression of wild-type DAF-16 modestly increases lifespan by 20% [11747825], while overexpression of constitutive nuclear forms of DAF-16 increases lifespan only slightly [11381260]. daf-16(mu86) mutation decreases mean (44%) and maximum (18%) lifespan [15905404]. daf-16(mgDf47) decreases mean (18-37%) and maximum (29%) lifespan [18828672]. daf-16 mutants are dauer defective [7219552] and completely suppress all the phenotypes of daf-2 and age-1 mutations, including lifespan extension, dauer arrest, reduced fertility, and viability defects [8247153; 7789761; 9504918; 7789761]. Mutations in daf-16 also suppress lifespan extension of animals that have a germ line ablation [10360574]. Sex-specific lifespan potential requires daf-16 [10747056]. daf-16 mutation suppresses enhanced UV resistance as well as increase longevity of daf-2, daf-23, spe-26, and clk-1 mutants. Mutation in daf-16 does not alter the reduced fertility in spe-26. daf-16 mutants are more fertile than wild-type [8807294]. 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
    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
    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
    pha-4 defective PHArynx development 4 pha-4 is required for multiple forms of DR. RNAi of pha-4 completely cancels out the lifespan extension of eat-2 mutation. Mutants of pha-4 do not respond to bacterial DR. Therefore, loss of pha-4 completely blocks the response to varying food concentration. Moreover, pha-4 expression is increased in response to DR in wild-type. pha-4 overexpression increases longevity of wild-type only slightly, but significant that of daf-16 mutants. The response to DR involves the PHA-4-dependent expression of sod-1, sod-2 and sod-5. Reduction of pha-4 does not suppress the long lifespan of daf-2 mutants or animals with defective electron transport chain [17476212]. IF significantly extends lifespan of pha-4 [19079239]. sDR extends lifespan of mutants with a temperature sensitive allele of pha-4 or pha-4 RNAi knockdown, but not daf-16 RNAi [19239417]. PHA-4 may play a role in the life-extending effects of dietary restriction. RNAi of pha-4 decreases lifespan of wild-type worms, but not of daf-2 mutants or of animals with defective electron transport chains. 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
    pnc-1 Pyrazinamidase and NiCotinamidase 1 pnc-1 knockdown by RNAi decreases maximum lifespan by 30%. Overexpression of pnc-1 increases adult survival under oxidative stress but does not extend the lifespan [17335870]. 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
    rab-5 RAB family 5 rab-5 RNAi in the adulthood reduces mean and maximum lifespan by 38 and 50% [23144747]. 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
    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
    lin-40 abnormal cell LINeage 40 RNA interference decreases median lifespan by 24% in wild-type animals, 38% in a daf-2 background and 24% in daf-2/daf-16 double mutants [18006689]. 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
    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
    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
    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
    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
    Factors are an extension of GenAge and GenDR.

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