Cellular senescence in ageing: from mechanisms to therapeutic opportunities

Author: Raffaella Di Micco1, Valery Krizhanovsky2, Darren Baker3,4, Fabrizio d'Adda di Fagagna5,6
Affiliation: <sup>1</sup> San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute, Milan, Italy. dimicco.raffaella@hsr.it. <sup>2</sup> Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel. <sup>3</sup> Department of Pediatrics, Mayo Clinic, Rochester, MN, USA. <sup>4</sup> Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA. <sup>5</sup> IFOM - The FIRC Institute of Molecular Oncology, Milan, Italy. fabrizio.dadda@ifom.eu. <sup>6</sup> Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, Pavia, Italy. fabrizio.dadda@ifom.eu.
Conference/Journal: Nat Rev Mol Cell Biol
Date published: 2020 Dec 16
Other: Special Notes: doi: 10.1038/s41580-020-00314-w. , Word Count: 146


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.


PMID: 33328614 DOI: 10.1038/s41580-020-00314-w