Cellular senescence at the bidirectional interface between ageing and coronary artery disease

Coronary artery disease (CAD) is a major global cause of morbidity and mortality, and population ageing is reshaping its clinical phenotype, disease trajectory, and therapeutic complexity. Chronological age alone cannot explain the heterogeneity of CAD outcomes in older individuals, highlighting the need to integrate biological ageing into cardiovascular disease research and management. Cellular senescence, characterised by stable cell-cycle arrest, metabolic reprogramming, and acquisition of a senescence-associated secretory phenotype (SASP), provides a mechanistic bridge between ageing and CAD. Senescent endothelial cells, vascular smooth muscle cells, immune cells, fibroblasts, and cardiomyocytes contribute to endothelial dysfunction, chronic inflammation, plaque instability, impaired myocardial stress tolerance, and adverse remodelling. Conversely, CAD-related stressors, including atherosclerotic injury, disturbed flow, myocardial ischaemia and ischaemia-reperfusion injury, can induce local senescence programmes and propagate inflammatory or extracellular-vesicle-mediated signalling beyond the initial injury site. However, whether CAD directly accelerates whole-organism biological ageing remains less established. In this review, we examine cellular senescence as a bidirectional but context-dependent interface between ageing and CAD. We summarise cell-type-specific senescence programmes in vascular and myocardial compartments, compare the strength of evidence for major molecular pathways, and discuss senescence-targeted therapies. We emphasise that senolytic and senomorphic strategies remain largely preclinical in cardiovascular disease and that their translation will require careful attention to disease stage, treatment timing, cell specificity and patient stratification. This framework may help refine ageing-informed approaches to CAD prevention, diagnosis and therapy.