The role of cellular senescence in cardiac disease: basic biology and clinical relevance

In this Review, Nattel and colleagues discuss the role of cellular senescence in cardiac disease, summarize the therapeutic strategies that are being developed for targeting senescence and consider the potential implications for improving the management of patients with heart disease. Cellular senescence, classically defined as stable cell cycle arrest, is implicated in biological processes such as embryogenesis, wound healing and ageing. Senescent cells have a complex senescence-associated secretory phenotype (SASP), involving a range of pro-inflammatory factors with important paracrine and autocrine effects on cell and tissue biology. Clinical evidence and experimental studies link cellular senescence, senescent cell accumulation, and the production and release of SASP components with age-related cardiac pathologies such as heart failure, myocardial ischaemia and infarction, and cancer chemotherapy-related cardiotoxicity. However, the precise role of senescent cells in these conditions is unclear and, in some instances, both detrimental and beneficial effects have been reported. The involvement of cellular senescence in other important entities, such as cardiac arrhythmias and remodelling, is poorly understood. In this Review, we summarize the basic biology of cellular senescence and discuss what is known about the role of cellular senescence and the SASP in heart disease. We then consider the various approaches that are being developed to prevent the accumulation of senescent cells and their consequences. Many of these strategies are applicable in vivo and some are being investigated for non-cardiac indications in clinical trials. We end by considering important knowledge gaps, directions for future research and the potential implications for improving the management of patients with heart disease.

Automated summary

This review discusses the role of cellular senescence in cardiac disease, outlines therapeutic strategies for targeting senescence, and considers potential implications for improving the management of patients with heart disease. The complex senescence-associated secretory phenotype (SASP) of senescent cells has important effects on cell and tissue biology. Future research is needed to better understand the precise role of senescent cells in various cardiac pathologies and develop strategies for preventing their accumulation.