The Role of the Senescence-Associated Secretory Phenotype in Cardiovascular Disease Among the Elderly

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in the elderly, driven not only by traditional risk factors but also by biological aging processes such as cellular senescence. Senescent cells accumulate in cardiovascular tissues with age and secrete a complex mix of pro-inflammatory cytokines, chemokines, proteases, and growth factors known as the senescence-associated secretory phenotype (SASP). While SASP may play beneficial roles in tissue repair, its chronic activity drives systemic inflammation, vascular remodeling, endothelial dysfunction, and myocardial fibrosis—all key features of age-related CVD. This review synthesizes the current understanding of SASP’s mechanistic contributions to vascular aging, atherosclerosis, heart failure, and arrhythmias in older adults. It highlights how SASP promotes arterial stiffness, plaque instability, cardiac remodeling, and electrical conduction abnormalities. Furthermore, the review explores emerging therapeutic strategies targeting SASP, including senolytics and senomorphics, and discusses their potential to mitigate age-related CVD. We also examine biomarker development and outline key knowledge gaps, emphasizing the need for longitudinal human studies to guide precision senescence-targeted therapies in elderly cardiovascular populations.