Abstract
Aging is a complex, multifaceted process affecting all organ systems, with vascular aging playing a central role in organismal health decline. Beyond its role in circulation, the vascular system acts as a dynamic interface between tissues, influencing countless physiological functions such as tissue regeneration and repair, immune responses, and metabolic balance. Importantly, age-related vascular impairment-characterized by a peculiar set of endothelial aging hallmarks-exacerbates age-related diseases (ARDs) such as cardiovascular disorders, neurodegeneration, chronic kidney disease, sarcopenia, and osteoporosis. This review combines basic concepts of angioscience and aging biology with translational interventions to devise clinical strategies promoting a functional rejuvenation of old and compromised blood vessels, fostering the prevention, delay or treatment of ARDs. Starting from the description of the cellular and molecular mechanisms driving vascular aging, a cutting-edge perspective on the organ-specific vascular impairment and its impact on tissue function is offered. Given the central role of the vasculature in aging, how targeting vascular aging through pharmacological, genetic, and lifestyle interventions holds promise for mitigating its systemic consequences and improving healthspan is discussed. Finally, how the combination of animal models (e.g., parabiosis) and novel microphysiological systems, coupled with multi-omics and artificial intelligence-driven analyses, is advancing the field toward the identification of strategies that promote vascular resilience and extend healthspan, addressing one of the most pressing biomedical challenges of a worldwide aging population is highlighted.