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Lookup NU author(s): Dr Anna Walaszczyk, Emily Dookun, Dr Rachael Redgrave, Dr Simon Tual-ChalotORCiD, Professor Ioakim SpyridopoulosORCiD, Dr Andrew OwensORCiD, Professor Helen ArthurORCiD, Dr Joao Passos, Professor Gavin RichardsonORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Cardiovascular disease is the leading cause of death in individuals over 60 years old. Ageing is associated with an increased prevalence of coronary artery disease and a poorer prognosis following acute myocardial infarction (MI). With age, senescent cells accumulate in tissues, including the heart, and contribute to age-related pathologies. However, the role of senescence in recovery following MI has not been investigated. In this study, we demonstrate that treatment of aged mice with the senolytic drug, navitoclax, eliminates senescent cardiomyocytes and attenuates pro-fibrotic protein expression in aged mice. Importantly, clearance of senescent cells improved myocardial remodelling and diastolic function as well as overall survival following MI. These data provide proof-of-concept evidence that senescent cells are major contributors to impaired function and increased mortality following MI and that senolytics are a potential new therapeutic avenue for MI.
Author(s): Walaszczyk A, Dookun E, Redgrave R, Tual-Chalot A, Spyridopoulos I, Owens A, Arthur HM, Passos JF, Richardson GD
Publication type: Article
Publication status: Published
Journal: Aging Cell
Year: 2019
Volume: 18
Issue: 3
Print publication date: 01/06/2019
Online publication date: 28/03/2019
Acceptance date: 17/02/2019
Date deposited: 28/03/2019
ISSN (print): 1474-9718
ISSN (electronic): 1474-9726
Publisher: Wiley-Blackwell Publishing Ltd.
URL: https://doi.org/10.1111/acel.12945
DOI: 10.1111/acel.12945
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