Senolysis in the senescent heart: A review of current literature

Abstract

Cellular senescence has been established as a fundamental biological mechanism in the pathogenesis of age-related cardiovascular diseases (CVD). The accumulation of senescent cells drives chronic inflammation and tissue dysfunction. Senolytic therapy, focused on the selective elimination of these cells, is emerging as a promising therapeutic strategy. Objective: The objective of this review is to justify senolytic therapy as a potential treatment for CVD by analyzing available preclinical evidence and proposing research lines adapted to the Venezuelan reality. Methodology: Narrative literature review (2015-2025) in databases (PubMed, Google Scholar), using keywords such as "Senescence," "CVD," and "Senolytics." Results: The evidence, derived from experimental studies (preclinical), demonstrates that senolytic agents (such as the Dasatinib + Quercetin combination, Fisetin, and Navitoclax) effectively reverse endothelial dysfunction, myocardial fibrosis and improve cardiac function. However, clinical translation faces significant barriers, mainly the known toxicity of the most potent agents (e.g., thrombocytopenia from Navitoclax, myelosuppression from Dasatinib), derived from their oncological use. Conclusion: Senolytic therapy represents a frontier in preventive medicine, with the potential to avoid the appearance of senescent cells and, consequently, the development of cardiovascular disease. It is concluded that initiating local research in Venezuela, focused on the use of indirect SASP biomarkers and cost-effectiveness analyses, is essential to adapt this therapy to the national context.