Vascular aging as a driver of thrombosis in older adults: From mechanisms to gerotherapeutics

With increasing chronological age, the vascular system gradually loses its functional integrity, a process known as vascular aging. This decline is a major contributor to arterial and venous thromboembolic disorders, which represent one of the leading causes of mortality and morbidity among aged individuals. However, the precise biological mechanisms linking systemic aging to thrombotic susceptibility remain poorly understood, hindering the development of effective preventive and therapeutic strategies for age-related thrombotic diseases. Aging, as a fundamental determinant of vascular health, shifts the balance between prothrombotic and antithrombotic mechanisms through cumulative molecular and cellular alterations across vascular cells, red blood cells, platelets, and immune cells. These interconnected hallmarks collectively disrupt endothelial homeostasis, enhance platelet reactivity, and impair coagulation and fibrinolytic pathways. Emerging factors, including clonal hematopoiesis of indeterminate potential and environmental exposures, further exacerbate the thrombotic risk in older populations. Clinically, thrombosis management in the elderly requires careful calibration between protection against ischemia and bleeding risk, as age-associated changes are known to affect the safety and efficacy of antiplatelet and anticoagulant therapies. The development of geroscience-guided interventions, alongside optimized antithrombotic strategies, will be essential to reduce the thrombotic burden and improve outcomes in the aging population.