Caveolin-1 at the nexus of endothelial aging and extracellular vesicle signaling.

Caveolin-1 (CAV1), the principal structural protein of caveolae, is a critical regulator of endothelial homeostasis, vascular aging, and frailty in older adults. By scaffolding multiple signaling pathways and controlling endothelial nitric oxide synthase activity, CAV1 shapes nitric oxide bioavailability, oxidative stress responses, and vascular stiffness. In parallel, extracellular vesicles (EVs) derived from endothelial cells, platelets, and other vascular cells act as key mediators of intercellular communication, propagating senescence, inflammation, and thrombosis across the vascular tree. This narrative review synthesizes current evidence on the CAV1-EV axis as a mechanistic nexus linking endothelial dysfunction, cardiovascular disease, and geriatric syndromes, with a particular focus on frailty. We first summarize the structure, regulation, and post-translational modifications of CAV1, especially tyrosine-14 (Tyr-14) phosphorylation, and their impact on endothelial senescence and dysfunction. We then examine how CAV1 controls EV biogenesis, cargo loading, and uptake, and how CAV1-enriched EVs contribute to pro-inflammatory and prothrombotic phenotypes in aging and frail populations. Finally, we discuss the translational potential of CAV1-related EVs as circulating biomarkers for early vascular aging and as targets for geroscience-guided interventions, including engineered or mesenchymal stem cell-derived EVs with vasculoprotective cargo. By integrating molecular, vascular, and geriatric perspectives, this review proposes the CAV1-EV axis as a promising framework for risk stratification and vascular-targeted therapies aimed at preserving function and independence in older adults.