Pharmacological clearance of senescent cells improves survival and recovery in aged mice following acute myocardial infarction.
Anna WalaszczykEmily DookunRachael RedgraveSimon Tual-ChalotStella VictorelliIoakim SpyridopoulosAndrew OwensHelen M ArthurJoão F PassosGavin D RichardsonPublished in: Aging cell (2019)
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.
Keyphrases
- induced apoptosis
- acute myocardial infarction
- cell cycle arrest
- cardiovascular disease
- coronary artery disease
- left ventricular
- percutaneous coronary intervention
- oxidative stress
- heart failure
- endothelial cells
- adipose tissue
- dna damage
- cell death
- blood pressure
- metabolic syndrome
- atrial fibrillation
- acute coronary syndrome
- artificial intelligence
- skeletal muscle
- climate change
- coronary artery bypass grafting
- drug induced
- replacement therapy
- deep learning