Why induce Cellular Senescence Rather than Apoptosis?

When cells become senescent in vitro they often become resistant to apoptotic stimuli in comparison to proliferating cells.  It can be speculated that if immune cells are necessary for eliminating senescent cells, the pro-survival phenotype of senescent cells may function to favor such elimination. In conjunction with regulating immune ligands and the secretory phenotype, persistent activation of the DDR, particularly double strand breaks (DSBs), may also promote a pro-survival response to facilitate DNA repair. However, if senescent cells are not removed by the immune system, this pro-survival phenotype inadvertently promotes their persistence in tissues.  Alternatively, the pro- survival phenotype of senescent cells may be an adaptive response mediated by stresses within the microenvironment to facilitate protection from further stress.



The question still arises as to why senescent cells may favor removal by the immune system rather than undergoing programmed cell death.  One plausible explanation could be related to the potential function of senescent cells during cellular repair following tissue damage.  During wound healing, senescent cells most likely play a positive role by (1) secreting chemo-attractants that recruit and activate immune cells to the site of injury, (2) secrete growth factors to stimulate cellular proliferation required for cellular replacement and protein synthesis and (3) the secretion of proteases to debride damaged tissue.  In addition, senescent cells may help to preserve tissue integrity during wound healing, that may otherwise be lost if cells underwent apoptosis, until such time that non- resident cells from other sources, such as stem cells are present to repopulate the tissue with functional cells.  In an orchestrated response, senescent cells would be subsequently eliminated by the immune system when no longer required.

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The main focus of ageing research is to prevent/combat age-related disease and disability, allowing everyone to live healthier lives for longer.