Vascular aging: A central driver of multimorbidity.

Abstract

The aging of the vasculature is a primary determinant of cardiovascular disease risk and a key contributor to organismal decline. While our understanding of its molecular underpinnings has grown exponentially, the translation of these discoveries into effective clinical interventions remains a major hurdle. This review provides a critical appraisal of the current state of vascular aging pharmacology. We first dissect the core pathogenic mechanisms, including epigenetic drift, chronic low-grade inflammation, and cellular senescence, highlighting clinically relevant targets such as the IL-1β pathway and senescent cell populations. We then systematically evaluate current and emerging therapeutic strategies, ranging from repurposed metabolic drugs (e.g., SGLT2 inhibitors) and mitochondrial antioxidants (e.g., MitoQ) to pioneering senolytic and gene therapies. A central focus is placed on the translational bottlenecks that impede progress: the discordance between animal models and human biology, the challenge of targeted drug delivery to the vascular wall, and the lack of validated surrogate endpoints for clinical trials. We conclude by outlining a strategic roadmap for the future, emphasizing the need for precision medicine approaches, innovative clinical trial designs, and the integration of liquid biopsy biomarkers to accelerate the development of therapies that genuinely promote vascular health and resilience.