September 23, 2026Nature Cardiovascular Research
Vascular aging as a driver of organ dysfunction and systemic aging
Key result
Microvascular aging drives systemic tissue dysfunction via altered angiocrine signaling, highlighting novel vascular rejuvenation targets.
Why the study?
Microvascular aging remains an emerging frontier with limited understanding of its role in tissue dysfunction and systemic aging despite advances in macrovascular aging research.
Key Points
- Synthesize recent insights into vascular aging mechanisms, emphasizing how microvascular decay orchestrates organ dysfunction and presenting emerging avenues for vascular rejuvenation.
- Narrative synthesis of single-cell and multiomic profiling studies characterizing cellular heterogeneity across vessel walls throughout lifespan.
- Evaluation of endothelial and mural cell communication networks, specifically angiocrine and pericrine signaling pathways across diverse organ systems.
- Microvascular aging actively dictates organ dysfunction through impaired angiocrine and pericrine signaling rather than serving merely as passive structural damage.
- Single-cell and multiomic profiling reveals organotypic vulnerabilities within the vasculature that drive distinct patterns of systemic functional decline.
- Targeting vessel wall cell heterogeneity and intercellular signaling pathways presents actionable therapeutic strategies for organ rejuvenation.
PICO
P
Population
Vascular aging
E
Exposure / Comparator
Microvascular aging
This review highlights the critical role of microvascular aging and intercellular signaling in driving organ dysfunction and systemic aging, suggesting new therapeutic avenues for vascular rejuvenation.
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Ageing is not a uniform process that affects the entire heart. Rather, it seems to originate in specific areas. This insight opens up new possibilities for targeted intervention where the damage occurs.”
DRDavid Rodriguez MoralesCardiovascular researcher, Goethe University Frankfurt
“Our data suggests that ageing of the heart begins, in a sense, in the blood vessels. These niches act like small hotspots that trigger inflammation and remodelling processes, which then spread to the entire organ.”
CFCarlos Fernandez-HernandoProfessor of Comparative Medicine, Yale School of Medicine
“I might be biased, but I think the vascular system is probably the most important organ to study. Most people in western societies still die from some form of cardiovascular disease. As we age, the vascular system is the first to begin to decline, impacting the function of all other systems.”
Implication
May inform vessel-targeted rejuvenation strategies in aging; hypothesis-generating and requires prospective trials before clinical adoption.
Abstract
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.
Discussion
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Cite This Study
Dimmeler et al. (2026) conducted a review in Vascular aging. Microvascular aging was evaluated. Microvascular aging drives tissue dysfunction and systemic decline through altered angiocrine and pericrine signaling mechanisms, revealing emerging therapeutic opportunities for vascular rejuvenation.