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Senescence and Senolytics in Cardiovascular disease: Promise and Potential Pitfalls

Lookup NU author(s): Dr Andrew Owens, Dr Anna Walaszczyk, Professor Ioakim Spyridopoulos, Dr Emily Dookun, Dr Gavin Richardson

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Ageing is the biggest risk factor for impaired cardiovascular health, with cardiovascular disease being the cause of death in 40% of individuals over 65 years old. Ageing is associated with an increased prevalence of atherosclerosis, coronary artery stenosis and subsequent myocardial infarction, thoracic aortic aneurysm, valvular heart disease and heart failure. An accumulation of senescence and increased inflammation, caused by the senescence-associated secretory phenotype, have been implicated in the aetiology and progression of these age-associated diseases. Recently it has been demonstrated that compounds targeting components of anti-apoptotic pathways expressed by senescent cells can preferentially induce senescence cells to apoptosis and have been termed senolytics. In this review, we discuss the evidence demonstrating that senescence contributes to cardiovascular disease, with a particular focus on studies that indicate the promise of senotherapy. Based on these data we suggest novel indications for senolytics as a treatment of cardiovascular diseases which have yet to be studied in the context of senotherapy. Finally, while the potential benefits are encouraging, several complications may result from senolytic treatment. We, therefore, consider these challenges in the context of the cardiovascular system.


Publication metadata

Author(s): Owens WA, Walaszczyk A, Spyridopoulos I, Dookun E, Richardson GD

Publication type: Review

Publication status: Published

Journal: Mechanisms of Ageing and Development

Year: 2021

Volume: 198

Print publication date: 01/09/2021

Online publication date: 06/07/2021

Acceptance date: 04/07/2021

ISSN (print): 0047-6374

ISSN (electronic): 1872-6216

URL: https://doi.org/10.1016/j.mad.2021.111540

DOI: 10.1016/j.mad.2021.111540


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