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
    Foxo3 House mouse
    IL6 interleukin 6 (interferon, beta 2) Human
    Chromosome 4 epithelial cell adhesion molecule Human
    ABP1 Actin Binding Protein 1 ABP1 deletion increases replicative lifespan by 30% in the alpha strain and decreases replicative lifespan by 20% in the a strain [18340043]. Deletion of ABP1 increases replicative lifespan by 20% in the alpha strain and decreases replicative lifespan by 20% in the a strain [19030232]. Budding yeast
    ACB1 Acyl-CoA-Binding 1 ACB1 deletion extends chronological lifespan under starvation/extreme DR. Similar heat-shock resistance and resistance to a very hight concentration of acetic acid (but not resistance to oxidative stress) was enhanced by the deletion of ACB1. Deletion of ACB1 in W303-1A and DBY746 genetic backgrounds on synthetic complete media causes severe growth defects and sightly shorter lifespan and also heat-sensitivity [20657825]. Budding yeast
    NEK4 NIMA (never in mitosis gene a)-related kinase 4 Age-related differential methylation of the genetic marker rs2230534 which is synonymous to the mutation in NEK4 is statistically significant association with age and aging rate [23177740]. Human
    JAKMIP3 Janus kinase and microtubule interacting protein 3 Age-related differential methylation of the genetic marker rs2818384 which is synonymous to the mutation in JAKMIP3 is statistically significant association with age and aging rate. JAKMIP3 has a *cis* association with the aging differential methylated marker cg05652533 [23177740]. Copy-number variants of JAKMIP3 are associated with glioblastoma [Xiong et al. 2010]. Xiong, M., Dong, H., Siu, H., Peng, G., Wang, Y., and Jin, L. (2010). Genome-Wide Association Studies of Copy Number Variation in Glioblastoma. Proceedings of the 4th International Conference on Bioinformatics and Biomedical Engineering (iCBBE), 1–4. Human
    GTPBP10 GTP-binding protein 10 (putative) Age-related differential methylation of the genetic marker rs42663, which is missense mutation in GTPBP10 is statistically significant association with age and aging rate. GTPB10 associates with cg27367526 in STEAP2 [23177740]. Human
    Mgat5 mannoside acetylglucosaminyltransferase 5 Although grossly normal at birth, knockout mice display multiple deficiencies with age including hypersensitivity to autoimmune disease, higher oxidative metabolism, resistance to weight-gain, and signs of early ageing such as osteoporosis, decreased muscle mass, and depletion of adult stem cells. Interestingly, Mgat5-/-Pten+/- and Mgat5+/-Pten+/- mutant mice showed a small but significant increase in lifespan when compared to Pten+/- mice, accompanied by an apparent delay in the inevitable development of cancer in Pten+/- mice. House mouse
    Arntl aryl hydrocarbon receptor nuclear translocator-like Arntl knockout mice display symptoms of premature aging including a shorter lifespan, sarcopenia, cataracts, less subcutaneous fat, and organ shrinkage [16847346]. House mouse
    Atm Ataxia telangiectasia mutated homolog (human) Atm-deficient mice are viable, retarded in growth, infertile (male produce no mature sperm and female no gametes), display neurological dysfunction, and exhibit severe defects in T cell maturation while going on to develop thymomas [8917548; 8689683]. The majority of mutant mice rapidly develop thymic lymphomas and die before 4 months of age [8843194]. Cells of Atm(-/-) mice exhibit slow growth also in culture and premature senescence, telomeres are extensively shortened in multiple tissues [8689683]. Mice mutant for Atm and Terc display progressive multi-organ system compromise and features of accelerated aging [12540856]. House mouse
    CCL11 chemokine (C-C motif) ligand 11 CCL11 exhibits an age-related increase in the plasma and cerebrospinal fluid from healthy human individuals between 20 and 90 years [21886162]. Human
    CCL11 chemokine (C-C motif) ligand 11 CCL11 is an age-related systemic factor associated with decreased neurogenesis. Relative levels of CCL11 increase in the plasma during aging an in young mice during Heterochronic Parabiosis [21886162]. House mouse
    CCL2 chemokine (C-C motif) ligand 2 CCL2 levels are evaluated in old unpaired and young heterochronic (with old animals) paired mice [21886162]. House mouse
    CCL2 chemokine (C-C motif) ligand 2 CCL2 levels in plasma increase with age and it is part of the senescence-associated secretory phenotype [19648977]. Human
    Cdkn2a cyclin-dependent kinase inhibitor 2A Cdkn2a encodes different transcripts involved mostly in cell cycle regulation and cellular senescence [12882406], but it can also act as a tumor suppressor. Its expression level increase with age in rodents [15520862]. super-Ink4a/Arf mice carrying a transgenic copy of a large genomic segment containing an intact and complete copy of the Cdkn2a (a.k.a. Ink4a/Arf) gene are significantly protected from cancer and had no indication of accelerated aging. Cells derived from super-Ink4a/Arf mice have increased resistance to in vitro immortalization and oncogenic transformation [15520276]. Loss of Cdkn2a in mice results in tumour susceptibility [11544530]. Mice deficient in Cdkn2a have smaller age-related decline in self-renewal potential as this process is associated with increasing levels of Cdkn2a [16957738]. Increased levels of p16 are associated with aging (Krishnamurthy et al., 2006; Molofsky et al., 2006) and a bona fide marker of cellular senescence (Collado et al., 2007). p16INK4a accumulates in many tissues as a function of advancing age (Krishnamurthy et al., 2004; Nielsen et al., 1999; Zindy et al., 1997) and is an effector of senescence (Campisi, 2003; Park et al., 2004), p16INK4a is a potent inhibitor of proliferative kinase Cdk4 (Lowe and Sherr, 2003) which is essential for pancreatic ?-cell proliferation in adult mammals (Rane et al., 1999; Tsutsui et al., 1999). p16INK4a constrains islet proliferation and regeneration in an age-dependent manner. Expression of the p16INK4a transcript is enriched in purified islets compared with the exocrine pancreas and islet-specific expression of p16INK4a increases markedly with aging (Krishnamurthy et al., 2006). Aging in mammals is associated with reduced regenerative capacity in tissues that contain stem cells (Chien and Karsenty, 2005) which is probably partially caused by senescence of progenitors with age (Campisi, 2005; Lombard et al., 2005). Progenitor proliferation in subventricular zone and neurogenesis in the olfactory bulb as well as multipotent progenitor frequency and self-renewal potential, all decline with ageing the mouse forebrain. The decline in progenitor frequency and function correlate with increased expression of p16INK4a (Molofsky et al., 2006). Aging p16INK4a-deficient mice exhibit a significantly smaller decline in subventricular zone proliferation, olfactory bulb neurogenesis and the frequency and self-renewal potential of multipotent progenitors (Molofsky et al., 2006). p16 expression in skin cells is significantly lower the the group that has a strong family history of longevity. As such a younger biological age associates with lower levels of p16INKfa positive cells [22612594]. p16 expression increases exponentially with age. Expression of p16INK4a with age does not predict cancer development. p16INK4a activation is a characteristic of all emerging cancers [http://denigma.de/url/3n]. House mouse
    CTA1 CaTalase A 1 CTA1 overexpression partially suppresses the shortened chronological lifespan by ISC1 mutation [21707788]. Budding yeast
    dcp-66 Deacetylase Complex Protein 66 dcp-66 RNAi shortens the mean lifespan by 29% and suppresses lifespan extension by isp-1 mutation, but does not significantly affect lifespan extension neither by eat-2 nor daf-2 mutation [22829775]. Nematode
    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
    FAR11 Factor ARrest 3 Deletion of FAR11 significantly reduces mean chronological lifespan under starvation/extreme DR relatively to wild-type [20657825]. Budding yeast
    FAR3 Factor ARrest 3 Deletion of FAR3 significantly reduces mean chronological lifespan under starvation/extreme DR relatively to wild-type [20657825]. Budding yeast
    FCY1 FluoroCYtosine resistance 1 Deletion of FCY1 does non-significantly decrease mean and maximum replicative lifespan by 4% and 8%, respectively [20550517]. Budding yeast
    Foxm1 Forkhead box M1 Deletion of Foxm1 causes age-related deterioration in liver regeneration. Increased hepatocyte expression in 12-month-old (aged) transgenic mice of Foxm1b alone is sufficient to restore hepatocyte proliferation to levels found in 2-month-old (young) regenerating liver [14647066]. House mouse
    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
    IDP3 Isocitrate Dehydrogenase, NADP-specific 3 Deletion of IDP3 results in a replicative lifespan increase by 15% in the alpha strain and decrease by 20% in the a strain [18340043; 19030232]. Budding yeast
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    • 25 of 99 factors
    Factors are an extension of GenAge and GenDR.

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