TY - JOUR
T1 - Cellular senescence in ageing
T2 - from mechanisms to therapeutic opportunities
AU - Di Micco, Raffaella
AU - Krizhanovsky, Valery
AU - Baker, Darren
AU - d’Adda di Fagagna, Fabrizio
N1 - Publisher Copyright:
© 2020, Springer Nature Limited.
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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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U2 - 10.1038/s41580-020-00314-w
DO - 10.1038/s41580-020-00314-w
M3 - Review article
C2 - 33328614
AN - SCOPUS:85097621428
SN - 1471-0072
VL - 22
SP - 75
EP - 95
JO - Nature Reviews Molecular Cell Biology
JF - Nature Reviews Molecular Cell Biology
IS - 2
ER -