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
    BRE5 BREfeldin A sensitivity 5 Deletion of BRE5 increases mean replicative lifespan by 30% [16293764] and mean chronological lifespan in diploid cells [21447998] Budding yeast
    CCR4 Carbon Catabolite Repression 4 Deletion of CCR4 increases mean chronological lifespan by 20 - 41% (20, 33, 41) in diploid cells [21447998]. In W303R CCR4 deletion shortens replicative lifespan by approximately 80% and results in temperature sensitivity that is suppressed by SSD1-V. SSD1-V partially suppresses the short-lifespan of ccr4 mutant. CCR4 mutation is synthetically lethal in combination with deletion of MPT5 in the absence of SSD1-V [11805047]. Budding yeast
    Cdkn1a Cyclin-dependent kinase inhibitor 1A Deletion of Cdkna1 (alias p21) prolongs the lifespan of telomerase-deficient mice with dysfunctional telomeres and improves the repopulation capacity and self-renewal of hematopoietic stem cells [17143283]. The p21(-/-) strains like the Cdkn1a(tmi/Tyj) exhibits enormous regenerative capacities as it closes ear holes similar to MRL mice [20231440; 21722344]. House mouse
    CPR7 Cyclosporin-sensitive Proline Rotamase 7 Deletion of CPR7 has no effect on lifespan replicative lifespan, but increases chronological lifespan [11361336] Budding yeast
    CRC1 CaRnitine Carrier 1 Deletion of CRC1 increases replicative lifespan [16293764]. CRC1 deletion increases replicative lifespan by 25% in the alpha strain [19030232] Budding yeast
    CSR2 Chs5 Spa2 Rescue 2 Deletion of CSR2 results in higher levels of intracellular reactive oxygen species, augmentation of scavenging enzymes and extends replicative as well as chronological lifespan [16336970]. Budding yeast
    CTF8 Chromosome Transmission Fidelity 8 Deletion of CTF8 increases mean chronological lifespan by 15-92% (15, 18, 42, 45, 92) in diploid cells [21447998]. Budding yeast
    CUP9 Homeodomain-containing transcriptional repressor of PTR2, which encodes a major peptide transporter; imported peptides activate ubiquitin-dependent proteolysis, resulting in degradation of Cup9p and de-repression of PTR2 transcription Deletion of CUP9 increases replicative lifespan by 30% in the alpha and a strains [18340043]. Although CPU9 was identified as a potential long-lived mutant strain in a bar-code screen, the chronological lifespan of CUP9 deletion mutant is not significantly different from than of wild-type under starvation/extreme DR [20657825]. Budding yeast
    DNM1 Dnm1p Deletion of DNM1 extends significantly mean and maximum lifespan by 49 and 111% in FY10 strain and by 15 and 12% in BY4741 strain [17173038]. Budding yeast
    ERG5 ERGosterol biosynthesis 5 Deletion of ERG5 decreases replicative lifespan by 35% in the a strain [18340043], but increases mean chronological lifespan by 26 - 116% (26, 40, 43, 62, 116) in diploid cells [21447998]. Deletion of ERG5 cancels out the replicative lifespan extension of 0.5% glucose restriction [18690010]. Budding yeast
    FBP1 Fructose-1,6-BisPhosphatase 1 Deletion of FBP1 increases survival during the first 15 days during chronologocal aging, but does not increase chronological lifespan. FBP1 deletion reduces production of reactive oxygen species while overexpression of FBP1 shortens chronological lifespan [16199065]. Budding yeast
    GCN4 Transcriptional activator of amino acid biosynthetic genes in response to amino acid starvation; expression is tightly regulated at both the transcriptional and translational levels Deletion of GCN4 increases the replicative lifespan by 10% in the alpha strain [19030232]. GCN4 deletion decreases the lifespan in the alpha and a strain [20657825]. The chronological lifespan of GCN4 deletion is strongly decreased in the a strain [20421943]. Budding yeast
    GIS1 GIg1-2 Suppressor 1 Deletion of GIS1 increases replicative lifespan by 25% in the alpha strain [19030232] and causes major although not complete reversion of chronological lifespan extension by 0.5% glucose restriction [18225956]. Budding yeast
    GLN3 GLutamiNe metabolism 3 Deletion of GLN3 extends chronological lifespan [16418483]. GLN3 deletion decreases replicative lifespan by 20% in the alpha strain [19030232]. GLN3 deletion in the vineyard strain dramatically shortens chronological lifespan, while extends that of the laboratory strain [21901113]. Budding yeast
    GPA2 G Protein Alpha subunit 2 Deletion of GPA2 increases mean and maximum replicative lifespan by 40% and 26%, respectively [11000115]. Deletion of GPA2 extends replicative lifespan by reducing cAMP-PKA activity and provides a genetic model for DR [11000115]. Budding yeast
    GPR1 G-Protein coupled Receptor 1 Deletion of GRP1 increases mean and maximum replicative lifespan by 41% and 26%, respectively. GRP1 deletion mutants have also longer chronological lifespan. Deletion of GPR1 extends replicative lifespan by reducing cAMP-PKA activity and provides a genetically model for DR [11000115]. Budding yeast
    HAC1 Homologous to Atf/Creb1 1 Deletion of HAC1 decreases mean, median and maximum replicative lifespan by 10, 8 and 5%, respectively [23167605]. Budding 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
    HXK2 HeXoKinase 2 Deletion of HXK2 extends mean and maximum replicative lifespan by about 53% and 33%, respectively. Limiting glucose availability by mutating HXK2 significantly extends replicative lifespan and provides a genetically model of DR [11000115]. HXK2 deletion increases oxygene consumption. Changes in gene expression HXK2 mutation are quite similar to those of dietary-restricted cells. In fact, HXK2 mutants have a transcriptional profile that significantly resembles DR cells and cell overexpressing HAP4 [12124627]. Budding yeast
    INM1 INositol Monophosphatase 1 Deletion of INM1 increases replicative lifespan [16293764]. INM1 deletion results in an replicative lifespan increase by 50% in the alpha strain and a decrease by 10% in a strain [19030232]. Budding yeast
    INP51 INositol polyphosphate 5-Phosphatase 51 Deletion of INP51 increases replicative lifespan by 10% in the alpha strain and in a strain [18340043; 19030232]. Budding yeast
    INP53 Polyphosphatidylinositol phosphatase, dephosphorylates multiple phosphatidylinositols; involved in trans Golgi network-to-early endosome pathway; hyperosmotic stress causes translocation to actin patches; contains Sac1 and 5-ptase domains Deletion of INP53 increases mean replicative lifespan by 31% [16293764]. INP53 deletion increases replicative lifespan by 31% in the alpha strain and by 10% in the a strain [18340043]. Budding yeast
    Insr Insulin receptor Deletion of Insr specifically in adipose tissue results in a 15-18% increase in mean, median and maximum lifespan. Fat-specific insulin-receptor knockout (FIRKO) reduces fat mass and protects against age-related obesity and its subsequent metabolic abnormality, without an decrease in food intake. Both male and female FIRKO mice have an increase in mean lifespan of around 134 days (18%), with parallel increases in median and maximum lifespan. FIRKO mice consume the same amount of food on per animal basis as control littermates, but have 15-25% lower body-mass and 50-70% reduced fat mass [12543978]. Disruption of Insr in all tissues reults in neonatal lethality [8612577]. House mouse
    IPK1 Inositol Polyphosphate Kinase 1 Deletion of IPK1 increases mean replicative lifespan by 41 - 40% in the alpha strain [16293764; 19030232]. IPK1 deletion extends mean and maximum replicative lifespan by 24 and 19%, respectively, and was non-synergistic with moderate DR [21584246]. Budding yeast
    IRC14 Deletion of IRC14 increases mean replicative lifespan by 14-22% [16293764]. IRC14 is a dubious ORF overlapping IDH2. Budding yeast
    Factors are an extension of GenAge and GenDR.

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