Vascular senescence and aging: mechanisms, clinical implications, and therapeutic prospects

Abstract

The aging vasculature is characterized by endothelial dysfunction, arterial stiffness, and increased susceptibility to vascular pathologies. Central to these changes is the process of cellular senescence, where endothelial and vascular smooth muscle cells lose their replicative and functional capacity and adopt a pro-inflammatory secretory phenotype. This review provides an overview of the key mechanisms underlying vascular senescence, including the p53/p21 and p16/Rb pathways, the senescence-associated secretory phenotype (SASP), and oxidative stress, examines its contribution to cardiovascular diseases in older adults, and highlights emerging therapeutic strategies aimed at delaying or reversing these age-related vascular changes. In vascular cells, DNA damage, oxidative stress, and chronic inflammation associated with aging converge to amplify senescence. Clinically, vascular senescence is linked with hypertension, atherosclerosis, and increased overall cardiovascular risk. Several interventions, ranging from senolytics to lifestyle factors, show promise in mitigating these changes; however, long-term studies are needed. Given that vascular senescence is a pivotal driver of cardiovascular pathology in aging, targeting senescent cells or their secretory phenotype may potentially offer new avenues for preventing or attenuating age-related vascular diseases. This review presents an updated and integrative overview of vascular senescence, connecting fundamental cellular mechanisms with their clinical manifestations and highlighting the most promising therapeutic interventions.