Single-Cell Atlas Maps How Blood Vessel Linings Age Across the Human Body

Each heartbeat pushes blood through a vast network of vessels that carries oxygen, nutrients and other essential substances to every part of the body. These vessels are not just passive tubes. A thin layer of specialized endothelial cells lines their inner walls, regulating blood flow, controlling what passes into nearby tissues and helping coordinate responses to injury. These cells also support organ-specific roles, such as forming a protective barrier in the brain. With age, this system can become dysfunctional, raising susceptibility to cardiovascular disease and related mortality. 

Although endothelial cells are essential, aging studies often overlook them, and little is known about how they change over time. CeMM Principal Investigator Laura de Rooij and her team took up this question using single-cell analysis, which shows gene activity in individual endothelial cells rather than in blood vessels as a whole.

Their study, published in Nature Aging and led by first author Sarah Dobner, combined data from 34 existing studies. Together these covered more than 375,000 cells from 290 samples across 12 human tissues. By focusing on healthy or non-diseased tissues, the team aimed to find changes linked to aging rather than to diagnosed disease. The result is the Human Aging Endothelial Cell Atlas.

Cells lining veins, which can form sprouts that develop into new blood vessels, showed lower activity of several vessel-formation genes in older individuals. This could help explain why vessels may renew themselves less effectively with age, although the study did not measure repair capacity directly. In many tissues, genes linked to inflammation and to cellular senescence, a state in which cells stop dividing, were also more active.

“One of the most striking findings was that endothelial aging does not look the same across the vascular system. By bringing together data from different tissues, we could identify patterns that might have been missed by studying individual organs or endothelial cell types in isolation,” Dobner explains. 

The atlas also revealed age-related changes in genes that help endothelial cells turn mechanical signals, such as the force of flowing blood, into biological responses. In skin from older donors, YAP, a protein that helps cells respond to mechanical forces, was found more often inside endothelial cell nuclei. Whether this helps cells cope with aging or contributes to declining vessel function is still unclear.

The study has limitations. It compared people of different ages instead of following individuals over time, and information about donors’ lifestyles and medical histories was incomplete. Even so, the atlas and its accompanying interactive portal show that vascular aging is neither uniform nor simple.

“What excites me about this atlas is that it gives us a way to explore vascular aging across the human body, rather than treating all blood vessels as if they age in the same way. We now have a resource to help investigate which changes accompany endothelial aging, which may contribute to declining vascular function, and which could reflect how endothelial cells adapt to their changing environment,” de Rooij concludes.