Vascular aging as a driver of organ dysfunction and systemic aging

Centuries ago, Thomas Sydenham famously wrote, "A man is as old as his arteries", highlighting the importance of the vasculature for health and healthy aging. Here, we review recent developments in vascular aging research, focusing on how microvascular aging drives tissue dysfunction and the emerging therapeutic opportunities for vascular rejuvenation. Although macrovascular aging has long been studied, microvascular aging remains an emerging frontier. Recent single-cell and multiomic technologies now allow unprecedented resolution of vessel wall cellular and molecular heterogeneity across organs throughout life. Beyond angiogenesis, hemodynamics, barrier function, coagulation and inflammation, the vessel wall is increasingly recognized as an instructive gatekeeper of organ function: endothelial and mural cells actively control surrounding parenchyma via angiocrine and pericrine signaling mechanisms, controlling organ function in health and disease. Integrating these technological and conceptual advances has reshaped our understanding of vascular aging, revealing organotypic vulnerabilities and intercellular mechanisms that drive systemic decline.