Toggle Main Menu Toggle Search

Open Access padlockePrints

Pharmacological clearance of senescent cells improves survival and recovery in aged mice following acute myocardial infarction.

Lookup NU author(s): Dr Anna Walaszczyk, Emily Dookun, Dr Rachael Redgrave, Dr Simon Tual-Chalot, Professor Ioakim Spyridopoulos, Professor Helen Arthur, Dr Gavin Richardson

Downloads


Licence

This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

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.


Publication metadata

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

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


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share