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

Cardiovascular disease is the leading cause of death in individuals over 60 years old. Aging 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,...

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Autores principales: Walaszczyk, Anna, Dookun, Emily, Redgrave, Rachael, Tual‐Chalot, Simon, Victorelli, Stella, Spyridopoulos, Ioakim, Owens, Andrew, Arthur, Helen M., Passos, João F., Richardson, Gavin D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516151/
https://www.ncbi.nlm.nih.gov/pubmed/30920115
http://dx.doi.org/10.1111/acel.12945
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author Walaszczyk, Anna
Dookun, Emily
Redgrave, Rachael
Tual‐Chalot, Simon
Victorelli, Stella
Spyridopoulos, Ioakim
Owens, Andrew
Arthur, Helen M.
Passos, João F.
Richardson, Gavin D.
author_facet Walaszczyk, Anna
Dookun, Emily
Redgrave, Rachael
Tual‐Chalot, Simon
Victorelli, Stella
Spyridopoulos, Ioakim
Owens, Andrew
Arthur, Helen M.
Passos, João F.
Richardson, Gavin D.
author_sort Walaszczyk, Anna
collection PubMed
description Cardiovascular disease is the leading cause of death in individuals over 60 years old. Aging 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 profibrotic 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.
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spelling pubmed-65161512019-06-01 Pharmacological clearance of senescent cells improves survival and recovery in aged mice following acute myocardial infarction Walaszczyk, Anna Dookun, Emily Redgrave, Rachael Tual‐Chalot, Simon Victorelli, Stella Spyridopoulos, Ioakim Owens, Andrew Arthur, Helen M. Passos, João F. Richardson, Gavin D. Aging Cell Short Take Cardiovascular disease is the leading cause of death in individuals over 60 years old. Aging 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 profibrotic 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. John Wiley and Sons Inc. 2019-03-28 2019-06 /pmc/articles/PMC6516151/ /pubmed/30920115 http://dx.doi.org/10.1111/acel.12945 Text en © 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Short Take
Walaszczyk, Anna
Dookun, Emily
Redgrave, Rachael
Tual‐Chalot, Simon
Victorelli, Stella
Spyridopoulos, Ioakim
Owens, Andrew
Arthur, Helen M.
Passos, João F.
Richardson, Gavin D.
Pharmacological clearance of senescent cells improves survival and recovery in aged mice following acute myocardial infarction
title Pharmacological clearance of senescent cells improves survival and recovery in aged mice following acute myocardial infarction
title_full Pharmacological clearance of senescent cells improves survival and recovery in aged mice following acute myocardial infarction
title_fullStr Pharmacological clearance of senescent cells improves survival and recovery in aged mice following acute myocardial infarction
title_full_unstemmed Pharmacological clearance of senescent cells improves survival and recovery in aged mice following acute myocardial infarction
title_short Pharmacological clearance of senescent cells improves survival and recovery in aged mice following acute myocardial infarction
title_sort pharmacological clearance of senescent cells improves survival and recovery in aged mice following acute myocardial infarction
topic Short Take
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516151/
https://www.ncbi.nlm.nih.gov/pubmed/30920115
http://dx.doi.org/10.1111/acel.12945
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