TY - JOUR
T1 - Cellular senescence in ageing: from mechanisms to therapeutic opportunities
AU - Di Micco, Raffaella
AU - Krizhanovsky, Valery
AU - Baker, Darren
AU - di Fagagna, Fabrizio d'Adda
N1 - R.D.M. is supported by Telethon (TIGET grant E5), a Career Development Award from the Human Frontier Science Program, an Advanced Research Grant from the European Haematology Association, “Pilot and Seed Grant 2015” from San Raffaele Hospital, a Hollis Brownstein Research Grant from the Leukemia Research Foundation, the Interstellar Initiative on Healthy Longevity of the New York Academy of Sciences and the Japan Agency for Medical Research and Development, and the Italian AIRC under MFAG 2019, ID. 23321 project PI Di Micco Raffaella. V.K. is supported by grants from the European Research Council under the European Union’s Seventh Framework Proframme (309688) and under Horizon 2020 (856487), from the Israel Science Foundation (634-15; 2633-17), from the Israel Ministry of Health, Minerva Center “Ageing, from Physical Materials to Human Tissues”, and from the Sagol Institute for Longevity Research. V.K. is an incumbent of the Georg F. Duckwitz Professorial Chair. D.B. is supported by the Ellison Medical Foundation, the Glenn Foundation for Medical Research, the US National Institutes of Health (R01AG053229 and R01AG068076), the Mayo Clinic Children’s Research Center, the Alzheimer’s Disease Research Center at Mayo Clinic and the Cure Alzheimer’s Fund. F.d’A.d.F. is supported by AIRC (application 12971), Fondazione Telethon (GGP17111), PRIN 2015, the InterOmics Project, the AMANDA project Accordo Quadro Regione Lombardia-CNR, a European Research Council advanced grant (322726), a European Research Council proof-of-concept grant (875139), AriSLA (project “DDRNA and ALS”), the AIRC Special Program 5 per mille metastases (Project-21091) and the European Joint Programme on Rare Diseases (EJP RD).The authors apologize for not being able to cite all the important contributions of their colleagues owing to space limitations.
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.
UR - http://www.scopus.com/inward/record.url?scp=85097621428&partnerID=8YFLogxK
U2 - 10.1038/s41580-020-00314-w
DO - 10.1038/s41580-020-00314-w
M3 - مقالة مرجعية
C2 - 33328614
SN - 1471-0072
VL - 22
SP - 75
EP - 95
JO - Nature Reviews Molecular Cell Biology
JF - Nature Reviews Molecular Cell Biology
IS - 2
ER -