Cellular senescence in ageing: from mechanisms to therapeutic opportunities
Raffaella Di Micco, Valery Krizhanovsky, Darren Baker, Fabrizio d'Adda di Fagagna, Raffaella Di Micco, Valery Krizhanovsky, Darren Baker, Fabrizio d'Adda di Fagagna
Abstract
Cellular senescence, first described in vitro in 1961, has become a focus for biotech companies that target it to ameliorate a variety of human conditions. Eminently characterized by a permanent proliferation arrest, cellular senescence occurs in response to endogenous and exogenous stresses, including telomere dysfunction, oncogene activation and persistent DNA damage. Cellular senescence can also be a controlled programme occurring in diverse biological processes, including embryonic development. Senescent cell extrinsic activities, broadly related to the activation of a senescence-associated secretory phenotype, amplify the impact of cell-intrinsic proliferative arrest and contribute to impaired tissue regeneration, chronic age-associated diseases and organismal ageing. This Review discusses the mechanisms and modulators of cellular senescence establishment and induction of a senescence-associated secretory phenotype, and provides an overview of cellular senescence as an emerging opportunity to intervene through senolytic and senomorphic therapies in ageing and ageing-associated diseases.
Conflict of interest statement
Competing interests
D.B. is a co-inventor on patent applications licensed to or filed by Unity Biotechnology, a company developing senolytic medicines, including small molecules that selectively eliminate senescent cells. Research in the Baker laboratory has been reviewed by the Mayo Clinic Conflict of Interest Review Board and is being conducted in compliance with Mayo Clinic conflict of interest policies. V.K. is a co-inventor on patent applications in the field of senolytics, some of which are licensed to Sentaur Bio. F.d’A.d.F. is among the inventors on patent applications for the use of antisense oligonucleotides to target DNA damage-induced transcripts. R.D.M. declares no competing interests.
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Source: PubMed