Cardiovascular aging is characterized by progressive endothelial dysfunction and arterial stiffening, two interrelated processes underlying the increased risk of hypertension, coronary artery disease, heart failure, and atrial fibrillation in older individuals. Endothelial dysfunction results from reduced nitric oxide bioavailability, increased oxidative stress, chronic low-grade inflammation, and accumulation of senescent endothelial cells that secrete pro-inflammatory mediators. In parallel, structural alterations of the vascular wall, including elastin fragmentation, collagen deposition, cross-linking by advanced glycation end products, vascular smooth muscle cell phenotypic switching, and calcification, lead to increased stiffness and impaired vascular compliance. These maladaptive changes reinforce one another, creating a vicious cycle in which dysfunctional endothelium accelerates stiffening, while mechanical alterations in turn amplify endothelial injury. Molecular pathways involving NADPH oxidases, mitochondrial dysfunction, NF-κB, JAK/STAT, AMPK, mTOR, sirtuins, and epigenetic regulators integrate oxidative, inflammatory, and metabolic signals that shape vascular aging. Clinically, endothelial dysfunction and vascular stiffness predict cardiovascular events independent of traditional risk factors and serve as emerging biomarkers of biological vascular age. Established therapies such as statins, renin-angiotensin system blockade, structured exercise, and dietary interventions improve vascular function, while novel approaches targeting senescence and redox imbalance are under investigation. Understanding these mechanisms provides opportunities to mitigate vascular aging and extend cardiovascular health span.
Çelik et al. (Thu,) studied this question.