Cellular Senescence

Cellular senescence is the phenomenon by which normal diploid cells cease to divide. In culture, fibroblasts can reach a maximum of 50 cell divisions before becoming senescent. This phenomenon is known as “replicative senescence”, or the Hayflick limit. (1). Replicative senescence is the result of telomere shortening that ultimately triggers a DNA damage response. Cells can also be induced to senesce via DNA damage in response to elevated reactive oxygen species (ROS), activation of oncogenes and cell-cell fusion, independent of telomere length. As such, cellular senescence represents a change in “cell state” rather than a cell becoming “aged” as the name confusingly suggests.

Although senescent cells can no longer replicate,  they remain metabolically active and commonly adopt an immunogenic phenotype consisting of a pro-inflammatory secretome, the up-regulation of immune ligands, a pro-survival response, promiscuous gene expression (pGE) and stain positive for senescence-associated β-galactosidase activity. (2). The nucleus of senescent cells is characterized by senescence-associated heterochromatin foci (SAHF) and DNA segments with chromatin alterations reinforcing senescence (DNA-SCARS) (3) Senescent cells also affect tumour suppression, wound healing and possibly embryonic/placental development and a pathological role in age-related diseases. (4) For all of these reasons, cellular senescence is an essential mechanism that needs to be better known.

The experimental elimination of senescent cells from transgenic progeroid mice (5) and non-progeroid, naturally-aged mice (6) led to greater resistance against aging-associated diseases. There have been more mounting evidence that show the importance of this mechanism insofar as chronic diseases and aging are concerned. See blog-article on this topic.

Reference and Precision Notes


(1). 
Hayflick L; Moorhead PS (December 1961). “The serial cultivation of human diploid cell strains”. Exp. Cell Res. 25: 585–621.
(2).  Campisi, Judith (February 2013). “Aging, Cellular Senescence, and Cancer”. Annual Review of Physiology. 75: 685–705.
(3).  Rodier, F.; Campisi, J. (14 February 2011). “Four faces of cellular senescence”. The Journal of Cell Biology. 192 (4): 547–556.
(4). Burton, Dominick G. A.; Krizhanovsky, Valery (31 July 2014). “Physiological and pathological consequences of cellular senescence”. Cellular and Molecular Life Sciences. 71 (22): 4373–4386.
(5).  Baker, D.; Wijshake, T.; Tchkonia, T.; LeBrasseur, N.; Childs, B.; van de Sluis, B.; Kirkland, J.; van Deursen, J. (10 November 2011). “Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders”. Nature. 479: 232–6.
(6).  Xu, M; Palmer, AK; Ding, H; Weivoda, MM; Pirtskhalava, T; White, TA; Sepe, A; Johnson, KO; Stout, MB; Giorgadze, N; Jensen, MD; LeBrasseur, NK; Tchkonia, T; Kirkland, JL (2015). “Targeting senescent cells enhances adipogenesis and metabolic function in old age”. eLife.  See also Quick, Darren (February 3, 2016). “Clearing out damaged cells in mice extends lifespan by up to 35 percent”. www.gizmag.com. Retrieved 2016-02-04. See also Regalado, Antonio (February 3, 2016). “In New Anti-Aging Strategy, Clearing Out Old Cells Increases Life Span of Mice by 25 Percent”. And this source: Horvath S (2013). “DNA methylation age of human tissues and cell types”. Genome Biology. 14: R115.

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