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
    MIR27A microRNA 27a MIR27A can be both a tumor-suppressor and an oncogene. For instance, the expression of miR-27a is significantly lower in acute leukemia compared to normal cells. It has been shown that miRNA-27a inhibits cell growth and promotes apoptosis by targeting 14-3-3θ, a member of 14-3-3 family of anti-apoptotic proteins. [23236401]. Therefore, it acts as a tumor-suppressor in leukemia. However, in gastric cancer mir-27a acts as an oncogene by targeting inhibiting and thus promoting cancer cell growth [18789835]. Human
    miR152 microRNA 152 MiR152 belongs to miR148/152 cluster and can act as a tumor-suppressor. In ovarian cancer, miR152 suppresses DNMT1 directly and inhibits proliferation of cancer cells. [23318422] The miRNA is downregulated in ovarian cancer cells lines and its downregulation may lead to deregulation of cell proliferation in ovarian cancer. [21971665] Human
    miR148a microRNA 148a miR148a belongs to miR148-152 cluster and acts as a tumor-suppressor in different types of cancer. MiR148a expression is suppressed more than 4-fold in gastric cancer. An inverse correlation has been observed between miR148a expression and lymph node metastasis in gastric cancer. Mir148a suppresses migratory abilities of cancer cells and metastasis formation by downregulating the oncogene ROCK1 expression [21994419]. miR148a is downregulated in pancreatic ductal adenocarcinoma (PDAC). it has been shown that miR148a directly targets the 3'UTR region of CDC25B mRNA. CDC25B is a phosphatase that, by activating a cyclin-CDK complex, initiates mitosis, therefore CDC25B suppression by miR148a could have a tumor-suppressor effect on PDAC. [21709669] Human
    hsa-let-7c microRNA let-7c let-7c is downregulated in prostate cancer, which increases cell proliferation [22479342]. More specifically, let-7c is a regulator of androgen receptor (AR), which plays a role in the development of prostate cancer [22128178]. Human
    hsa-let-7b microRNA let-7b Let-7b, a member of the let-7 group, appears to be a tumor-suppressor. In acute lymphoblastic leukemia, let-7b is severely downregulated and its overexpression inhibits cancer cells growth [22918121]. In melanoma cells, the miRNA downregulates the expression of cell cycle regulators such as cyclin D1, D3, and A and Cdk4, which inhibits cell cycle progression. [18379589] Human
    hsa-let-7a microRNA let-7a A tumor-suppressor downregulated in different types of cancer. Let-7a binds to 3'-UTR region of RAB40C, thus leading to a decrease in cell proliferation and an increase of G1 arrest in human gastric carcinomas [20809749, 21349817]. In human breast cancer, evidence suggests that members of let-7 family inhibit breast cancer cell migration by targeting genes responsible for actin dynamics [23339187]. Moreover, let-7a directly targets CCR7, a receptor that promotes invasiveness of cancer cells [23335963] Human
    MIR145 microRNA 145 MIR145 is a tumor suppressor that acts by inhibiting IRS-1 in human colon cancer cells. It also targets IGFR1 [17827156; 19391107]. It decreases cell migration in gliomas by targeting CTGF, metastasis and migration-promoting gene. MIR145 is downregulated in astrocytic tumors and oligodendrogliomas [23390502; 23577178]. Human
    MIR15A microRNA 15a MIR15A is a tumor-suppressor downregulated in different types of cancers. In chronic lymphocytic leukemia (CLL) it is downregulated in 68% of cases [12434020]. MIR15A may post-transcriptionally downregulate the expression of Bcl2, thus inducing apoptosis. Therefore, inactivation of MIR15A and MIR16-1 in CLL lymphocytes results in a reduced apoptosis rate [16166262]. In prostate cancer, MIR15A and MIR16-1 are downregulated, which results in decreased repression of FGF-2, thus promoting tumor expansion and invasiveness [21532615]. MIR15A and MIR16-1 are also downregulated in pituitary adenomas as thier expression exhibits an inverse correlation with tumor diameter, therefore possible influence on tumor growth [15648093]. Human
    MIR29A microRNA 29a miR-29a reduces the amount of methylation and upregulates a long non-coding RNA form a region called MEG3 that is responsible for inducing apoptotic pathway. Thus reducing tumorgensis in non-malignant hepatocytes [21625215]. 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
    • 10 factors
    Factors are an extension of GenAge and GenDR.

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