Cellular senescence is the exhaustion of cell division potential [Hayflick & Moorhead]. ¶
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Senescent cells are present in aged tissues taken from variety of species, including mice, baboons and humans [Herbig et al. 2006; Jeyapalan et al. 2007; Wang et al 2009]. In fact tissues from aged aged animals are a mixture of senescent cells interspersed with normal cells (old, perhaps age-compromised cells but not yet senescent) [Bahar et al. 2006; Herbig et al. 2006]. The number of senescent fibroblasts increases exponentially with age in the skin of baboons. Senescent cells are over 15% of cells in very old animals [16456035]. Senescence cells are also present in mouse tissues such as in the liver [18440596]. ¶
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Senescence can be triggered by several stressors that result in molecular damage or simple by exhaustion of replicative potential [Adams 2009]. ¶
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Cellular senescence is characterized by biochemical events that occur with the cell leading to growth arrest as well as loss of specialized cellular functions [Campisi et al. 2002]. Senescent cells cannot divide, their ability to synthesize proteins is reduced, and the DNA repair system is attenuated [Hasty et al. 2003]. ¶
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Senescent cells impair tissue renwal and homeostasis, decrease organ funciton and contirbute to the aging phenotype. ¶
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Telomere shortening with age contribute to cancer susceptibilityby increasing the risk of chromosomal aberrations [11089982]. Mice with short telomeres have higher cancer incidence [10089885], including in mice deficient for p53 [10338216]. ¶
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Senescent cells secret pro-inflammatory cytokines and other factors that disrupt the tissue microenvironment and promote tumorigenesis. Immunocompromised mice injected with tumor-forming cells together with senesecent cells form more and larger tumors that tumour-forming cells alone or with presenescent cells [11593017; 20169192; 17409418]. Senescent cells derive a inflammatory network dependent of interleukins that promotes cancer [18555778]. ¶
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The clearance of senescent cells expression p16INK4a, although it does not extend the lifespan, delays aging-associated disorders in progeriod mice [22048312]. ¶
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Senescent human fibroblasts stimulate profileration of premalignant and malignant epithelial cells, but not of normal cells in cell culture [11593017]. ¶
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References ¶
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Hayflick, L. & Moorhead, P.S. (1961) The serial cultivation of human diploid cell strains. Exp. Cell Res. 25, 585–621. ¶
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Herbig, U., Ferreira, M., Condel, L., Carey, D. & Sedivy, J.M. (2006) Cellular senescence in aging primates. Science 311, 1257. ¶
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Jeyapalan, J.C., Ferreira, M., Sedivy, J.M. & Herbig, U. (2007) Accumulation of senescent cells in mitotic tissue of aging primates. Mech. Ageing Dev. 128, 36–44. ¶
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Wang, C., Jurk, D., Maddick, M., Nelson, G., Martin-Ruiz, C. & von Zglinicki, T. (2009) DNA damage response and cellular senescence in tissues of aging mice. Aging Cell 8, 311–323. ¶
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Bahar, R., Hartmann, C.H., Rodriguez, K.A., Denny, A.D., Busuttil, R.A., Dolle, M.E., Calder, R.B., Chisholm, G.B., Pollock, B.H., Klein, C.A. & Vijg, J. (2006) Increased cell-to-cell variation in gene expression in ageing mouse heart. Nature 441, 1011–1014. ¶
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Herbig, U., Ferreira, M., Condel, L., Carey, D. & Sedivy, J.M. (2006) Cellular senescence in aging primates. Science 311, 1257. ¶
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Adams, P.D. (2009) Healing and hurting: molecular mechanisms, functions, and pathologies of cellular senescence. Mol. Cell 36, 2–14. ¶
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Campisi J. Cancer and aging: yin, yang, and p53. Sci Aging Knowledge Environ. 2002;2002:pe1. ¶
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Hasty P, Campisi J, Hoeijmakers J, van Steeg H, Vijg J. Aging and genome maintenance: lessons from the mouse? Science. 2003;299:1355–1359. ¶