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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  • Types: + -
  • symbol name observation species
    asp-3 ASpartyl Protease 3 RNA interference against asp-3 significantly reduces lifespan of eat-2(ad1116) mutants, without any significant affect on the lifespan of wild-type. Mean and 75%ile lifespan of eat-2 mutants is reduced by 13-14% and 5-9% by asp-3 RNAi. ASP-3 is upregulated in eat-2 mutants [22810224]. Nematode
    acdh-1 Acyl CoA DeHydrogenase 1 RNAi knockdown of acdh-1 starting at hatching or only during the adulthood significantly decreases lifespan of eat-2 without affecting wild-type lifespan. ACDH-1 significantly upregulated in eat-2. Increased content of ACDH-1 is, at least partially, required for lifespan-extension by DR [22810224]. Nematode
    FET3 FErrous Transport 3 FET3 mutation slightly shortens chronological lifespan under AL. Its chronological lifespan is not extended by 0.5% glucose or amino-acid DR [20421943]. FET3 is one of several iron related genes that are up-regulated in response to increasing strength of glucose DR [18679056]. Budding yeast
    gpa2 Guanine nucleotide-binding protein alpha-2 subunit gpa2 (alias git8) encodes the alpha subunit of a heterotrimeric G protein, which acts downstream of Git3. Git8 activity accelerates aging and inhibits the lifespan-extending effect of DR. Constitutive active mutation of gpa2 decreases chronological lifespan under AL (2% glucose) and almost completely cancels out the lifespan extending effect of DR (0.2% glucose) [19266076]. Fission yeast
    HES1 Homologous to kES1 1 Deletion of HES1 (alias OSH5) extends replicative lifespan and is non-additive with moderate DR. Elevation of OSH5 levels by an ERG6 promoter reduces mean, median and maximum replicative lifespan by 25, 18 and 29%. HES1 is required for the longevity effect of DR, Perg6-OSH6, Perg6-ERG2 and Perg6-OSH7 (genetic mimetics of DR). Hes1 is upregulated in response to sterol down-regulation including DR. Deletion of OSH5 delays different steps of endocytosis, a sterol-requireing process [Xia et al., unpublished]. Perg6-OSH6 osh5 double mutant have a lifespan significantly shorter than that of Perg6-OSH6 [Xia et al. upublished]. Budding yeast
    PNC1 Pyrazinamidase/NiCotinamidase 1 Cells with 5 copies of PNC1 have a 70% longer replicative lifespan which is cancelled out by SIR2 deletion. PNC1 is upregulated under glucose DR [12736687]. Pnc1 reduces cellular nicotinamide levels, a product and noncompetitive inhibitor of Sir2 deacetylation reaction. Overexpression of PNC1 suppresses the effect of exogenously added nicotinamide on Sir2-dependent silencing at HM loci, telomeres and rDNA loci [12736687; 14729974]. Pnc1 catalyses the breakdown of nicotinamide to nicotinate and ammonia [12736687]. Deletion of PNC1 shortens replicative lifespan approximately by 10% [12736687] and largely prevents replicative lifespan extension of 0.5% glucose restriction. 0.5% glucose restriction slightly extends median replicative lifespan (by 10 - 15%) but not maximum replicative lifespan in pnc1Delta [14724176]. PNC1 overexpression suppresses the inhibitory effect of exogenously added NAM on silencing, lifespan, and Hst1-mediated transcriptional repression [14729974]. Increased expression of PNC1 is both necessary and sufficient for replicative lifespan extension by DR and low-intensity stress. Under non-stressing conditions (2% glucose, 30 degree Celsius), a strain with additional copies of PNC1 (5XPNC1) has 70% longer replicative lifespan than the wild-type and some cells live for more than 70 divisions. Neither DR nor heat stress further increase the lifespan of the 5XPNC1 strain [12736687]. PNC1 deletion decreases chronological lifespan [17110466]. Budding yeast
    sbds-1 Shwachman-Bodian-Diamond Syndrome protein homolog 1 RNA interference of sbds-1 decreases median lifespan by 24% in daf-2 mutants [18006689]. RNAi knockdown of sbds-1 starting at hatching or only during the adulthood significantly decreases lifespan of eat-2 without affecting wild-type lifespan. SBDS-1 are elevated in eat-2 mutants. Increased content of SBDS-1 is, at least partially, required for lifespan-extension by DR [22810224]. Nematode
    unc-52 UNCoordinated 52 RNA interference of unc-52 in adulthood extends mean lifespan by 11% [17411345]. RNAi knockdown of unc-52 starting at hatching or only during the adulthood significantly decreases lifespan of eat-2 without affecting wild-type lifespan. UNC-52 levels are elevated in eat-2 mutants. Increased content of UNC-52 is, at least partially, required for lifespan-extension by DR [22810224]. Nematode
    • 8 factors
    Factors are an extension of GenAge and GenDR.

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