Therapeutic Elimination of Senescent cells


The persistence and accumulation of senescent cells has been shown to potentially play a role in the pathophysiology of ageing and age-related disease. Therefore, the elimination of senescent cells from tissues has the potential to increase health-span and possibly even lifespan. For example, it was recently demonstrated that the elimination of p16- expressing cells in a transgenic mouse model delays age-associated disorders. As such, there are a number of therapeutic avenues of research that have the potential to eliminate senescent cells or prevent their accumulation. Firstly, telomerase activators could be used to extend telomere length, thereby extending the replicative capacity of cells and preventing RS. Secondly, cellular reprogramming refers to the potential of reverting senescent cells back to their normal functioning state. Alternatively, if quiescent cells inflicted with DNA damage convert to senescence when stimulated to proliferate, then eliminating such damage may prevent this conversion. Thirdly, if senescent cells indeed accumulate due to failure of removal by an ageing immune system, then enhancing the immune response to senescent cells may improve their elimination. Finally, identification of pharmacological compounds that can specifically induce programmed cell death in senescent cells will provide an effective means for targeting senescent cells regardless the reason of their presence. However, the potential use of future pharmacological compounds should be taken with caution, since senescent cells also play a beneficial role during wound healing. Prematurely eliminating senescent cells during tissue damage may impair the wound response. In fact, it can be speculated that a tradeoff may exist between senescent cell removal and wound healing, whereby enhanced senescent cell removal (and possibly slower ageing) results in a slower healing process (and increase risk of infectious disease). Future research will show if pharmacological elimination of senescent cells is a good avenue for treatment of age-related disorders and health-span extension.


Link: Physiological and pathological consequences of cellular senescence

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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.