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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,...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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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. |
format | Online Article Text |
id | pubmed-6516151 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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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