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
    BHB β-hydroxybutyrate β-hydroxybutyrate (βOHB), ketone body is produced during a prolonged low-caloric or ketonic diet. Low concentrations of βOHB helps protect cells from "oxidative stress". dietary restriction (DR) spurs βOHB production. βOHB is an endogenous and specific inhibitor of class I histone deacetylases (HDACs). Exogenous βOHB administration, fasting or DR increases global histone acetylation in mouse tissues. HDAC inhibition by βOHB is correlated with global changes in transcription, including oxidative stress factors Foxo3a and Mt2. Cells treated with βOHB have increased histone acetylation at Foxo3a and Mt2 promoters. Both Foxo3a and Mt2 are activated by selective depletion of HDAC1 and HDAC2. normally keeps a pair of genes, namely Foxo3a and Mt2 switched off [http://www.biocompare.com/Life-Science-News/126847-Gladstone-Scientists-Discover-Novel-Mechanism-By-Which-Calorie-Restriction-Influences-Longevity/; http://www.sciencemag.org/content/early/2012/12/05/science.1227166].
    C60 [60]fullerene Oral administration of C60 dissolved in olive oil (0.8 mg/ml) at reiterated doses (1.7 mg/kg of body weight) for just about 7 months to rats not only does not entail chronic toxicity but it almost doubles the lifespan. The effects on lifespan is mainly due to the attenuation of age-associated increases in oxidative stress. Dissolved C60 is absorbed by the gastro-intestinal tract and eliminated in a few tens of hours [22498298]. C60-olive oil can increase the mean, median and maximum lifespan by 114, 91 and 74%. C60-olive oil extends the lifespan of animals with a probability of 0.999 and 0.995 with respect to water and olive oil treatments, respectively [22498298]. The GSSG/GSH ratio of animals treated by C60-olive oil is significantly less (about twice as less) as compared to controls [22498298]. C60 solutions have a characteristic purple color. C60 can cross the blood-brain barrier [21787853]. The elimination process follows a non-urinary route as it is mainly eliminated through the bile ducts [16351219; 21787853]. C60 reacts inside the liver cells with vitamin A following a Diels-Alder like reaction both in mice and rats [16351219].
    zyg-11 ZYGote defective: embryonic lethal zyg-11 RNAi in the adulthood extends the lifespan [New longevity regulators]. Nematode
    Zw Zwischenferment Mean lifespan of G6PD overexpressor flies is extended in comparison with driver and responder controls, armadillo-GAL4 (up to 38%), Tubulin-GAL4 (up to 29%), C23-GAL4 (up to 27%), da-GAL4 (up to 24%), D42-GAL4 (up to 18%) and Appl-GAL4 (up to 16%). The maximum lifespan is also increased [18809674]. G6PD enzymatic activity as well as levels of NADPH, NADH, and the GSH/GSSG ration are increased [18809674]. Fruit fly
    ZWINT ZW10 interactor ZWINT was found to be associated with longevity [22279548]. Human
    Zmpste24 zinc metallopeptidase, STE24 homolog (S. cerevisiae) Knockout mice exhibit nuclear architecture abnormalities and signs of accelerated ageing. House mouse
    ztf-12 Zinc finger Transcription Factor family RNA interference of ztf-12 results in a shortened lifespan. ztf-12 is a target of daf-16 [16380712]. Nematode
    ZC395.10 Zinc finger Transcription Factor family ZC395.10 RNAi in the adulthood extends the lifespan [New longevity regulators]. Nematode
    ZNF331 zinc finger protein 331 ZNF331 was found to be associated with longevity [21782286]. Human
    zfp-1 Zinc Finger Protein RNA interference shortened lifespan. Nematode
    ZBTB20 zinc finger and BTB domain containing 20 ZBTB20 was found to be associated with longevity [22279548]. Human
    ZDS2 Zillion Different Screens 2 Deletion of ZDS2 decreases replicative lifespan by about 20% [10662670]. ZDS2 null mutation decreases rDNA silencing five-fold, increases silencing at a mutant HMR that lacks the Rap1-binding site in the HNR-E silencer three-fold, and has no effect on telomeric silencing. ZDS2 deletion decreases rDNA silencing, increases rDNA recombination, and increases level of phosphorylated Sir3 [10662670]. Budding yeast
    ZDS1 Zillion Different Screens 1 Deletion of ZDS1 increases replicative lifespan by 37% in a SIR3-dependent manner [10662670]. Null mutation in ZDS1 causes 100-fold decrease in telomeric silencing, a nine-fold increase in rDNA silencing, reduces rDNA recombination, and decreases Sir3 phosphorylation [10662670]. Budding yeast
    ZTA1 Zeta-crystallin homolog, found in the cytoplasm and nucleus; has similarity to E. coli quinone oxidoreductase and to human zeta-crystallin, which has quinone oxidoreductase activity Deletion of ZTA1 increases replicative lifespan by 15% in the alpha strain and decreased by 10% in the a strain [18340043]. Although ZTA1 was identified as a potential long-lived mutant strain in a bar-code screen, deletion of ZTA1 does not significantly affect chronological lifespan under starvation/extreme DR [20657825]. Budding yeast
    Yaf2 YY1 associated factor 2 Yaf2 is transcriptional upregulated in the cerebral cortex at the age 28 months under different longevity conditions such as under dietary restriction (DR) as well as in feeding switch regimens that result in extended lifespan, like early age switch to DR as well as the reverse switch under the influence of the DR-mimetic α-lipoic acid (i.e. DR switched to ad libitum+ lipoic acid) [Shona et al. 2013]. Norway rat
    YTHDF2 YTH domain family, member 2 A locus associated with human longevity corresponds to (TG)n microsatellite is located in the YTHDF2 gene. 412 participants of different ages, including 137 centenarians, were genotyped. The increased homozygosity in centenarians at this locus was confirmed, and observed a concomitantly increased frequency of the most frequent allele and the corresponding homozygous genotype. The same genotype was associated with increased YTHDF2 messenger RNA levels in immortalized lymphocytes. [16799135].YTHDF2 was found to be associated with longevity [16799135]. Human
    UTH1 yoUTH 1 Mutation in UTH1 increases replicative lifespan by approximately 15% [7859289]. UTH1 mutant has enhanced stress resistance to cold stress [7859289], heat shock [10870102], starvation [7859289], hydrogen peroxide, but is sensitive to paraquat and oxygen [9799359]. Budding yeast
    YVH1 Yeast vaccinia virus VH1 Homolog 1 Deletion of YVH1 increases replicative lifespan by 50% in the alpha strain [18340043]. Budding yeast
    YUH1 Yeast Ubiquitin Hydrolase 1 Deletion of YUH1 decreases replicative lifespan decreased 30% in the alpha strain [18340043]. Budding yeast
    sir-2.4 yeast SIR related 2.4 RNA interference against sir-2.4 or overexpression of SIR-2.4 do not change the mean or maximum lifespan. Neither sir-2.4 RNAi nor SIR-2.4 overexpression affects the increased lifespan of daf-2(e1370) mutants [Tishkoff et al. 2012]. Nematode
    sir-2.1 Yeast SIR related 1 sir-2.1 deletion slightly reduces lifespan of wild-type [16860373]. sir-2.1 overexpression extends lifespan by about 50% and this lifespan extension depends on DAF-16 activity as it is suppressed by mutation in daf-16 and it does not synergize with daf-2 [11242085]. sir-2.1 suppresses longevity of unc-13 and eat-2, but not daf-2 or unc-64 mutants. sir-2.1 is therefore partially required for lifespan extension from mutation of eat-2 [16860373], but is completely independent for lifespan extension from DR using a reduced feeding protocol [Kaeberlein et al. in press]. sDR increases lifespan of wild-type and sir-2.1 mutants to the same extent [19239417]. Overrexpression of sir-2.1 synergizes with TGF-beta mutation (daf-4 and daf-1) for dauer formation [11242085]. Nematode
    YPT7 Yeast Protein Two 7 YPT7 deletion decreases replicative lifespan by 15% in the alpha strain [18340043]. Deletion of YPT7 cancels out replicative lifespan extension of 0.5% glucose restriction and results under DR also into a shorter replicative lifespan than under AL [18690010]. Budding yeast
    YPT6 Yeast Protein Two 6 Deletion of YPT6 increases replicative lifespan by 20% [19030232]. YPT6 deletion increases replicative lifespan by 30% in the alpha strain and by 10% in the a strain [18340043]. Budding yeast
    YPT32 Yeast Protein Two 32 Deletion increases mean chronological lifespan by 13 - 45% (13, 17, 45) in diploid cells [21447998]. Budding yeast
    YPK1 Yeast Protein Kinase 1 Deletion of YPK1 decreases replicative lifespan by 20% in the alpha strain [18340043]. Budding yeast
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    • 25 of 2668 factors
    Factors are an extension of GenAge and GenDR.

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