Cellular senescence in ageing: from mechanisms to therapeutic opportunities

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.

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Affiliated Institutions

• Istituti di Ricovero e Cura a Carattere Scientifico IT
• The San Raffaele Telethon Institute for Gene Therapy IT
• IFOM IT
• Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
• Mayo Clinic in Arizona US
• Weizmann Institute of Science IL

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