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.