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

Anna Walaszczyk, Emily Dookun, Rachael Redgrave, Simon Tual-Chalot, Stella Victorelli, Ioakim Spyridopoulos, Andrew Owens, Helen M. Arthur, João F. Passos, Gavin D. Richardson

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere12945
JournalAging Cell
Volume18
Issue number3
DOIs
StatePublished - Jun 2019

Keywords

  • aging
  • cardiac
  • myocardial infarction
  • senescence
  • senolytics
  • survival

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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    Walaszczyk, A., Dookun, E., Redgrave, R., Tual-Chalot, S., Victorelli, S., Spyridopoulos, I., Owens, A., Arthur, H. M., Passos, J. F., & Richardson, G. D. (2019). Pharmacological clearance of senescent cells improves survival and recovery in aged mice following acute myocardial infarction. Aging Cell, 18(3), [e12945]. https://doi.org/10.1111/acel.12945