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Senescence and senolytics in cardiovascular disease: Promise and potential pitfalls
W Andrew Owens1, Anna Walaszczyk2, Ioakim Spyridopoulos2
1Biosciences Institute, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK; The James Cook University Hospital, Middlesbrough, UK.
Insights
Aging significantly increases cardiovascular disease risk. Senolytics, drugs targeting senescent cells, show promise for treating age-related heart conditions like atherosclerosis and heart failure, though challenges remain.
Area of Science:
- Cardiovascular Science
- Gerontology
- Cellular Biology
Background:
- Aging is the primary risk factor for cardiovascular diseases (CVDs), leading to 40% of deaths in individuals over 65.
- Age-related conditions such as atherosclerosis, myocardial infarction, and heart failure are linked to cellular senescence and inflammation.
- Senescence-associated secretory phenotype (SASP) contributes to the development and progression of age-related cardiovascular pathologies.
Purpose of the Study:
- To review the evidence linking cellular senescence to cardiovascular disease.
- To explore the therapeutic potential of senolytics in treating age-related cardiovascular conditions.
- To identify novel indications for senolytic therapy and discuss associated challenges.
Main Methods:
- Literature review of studies on senescence, cardiovascular disease, and senolytics.
- Analysis of evidence implicating senescence in the pathogenesis of atherosclerosis, heart failure, and other cardiovascular conditions.
- Discussion of senolytic mechanisms and their potential application in cardiovascular medicine.
Main Results:
- Cellular senescence and SASP are key contributors to the development and progression of various cardiovascular diseases.
- Senolytics, by selectively eliminating senescent cells, demonstrate therapeutic promise for cardiovascular conditions.
- Potential new applications for senolytics in treating conditions like thoracic aortic aneurysm and valvular heart disease are suggested.
Conclusions:
- Senescence plays a critical role in cardiovascular aging and disease.
- Senotherapy, using senolytics, offers a promising strategy for managing age-related cardiovascular diseases.
- Further research is needed to explore senolytic efficacy and safety for cardiovascular applications, addressing potential complications.
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.
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