Scientists create first human endothelial cell atlas mapping how blood vessels age

Researchers led by Laura de Rooij at the CeMM Research Center compiled the Human Aging Endothelial Cell Atlas using single-cell data from over 375,000 cells across 12 human tissues. Published in Nature Aging by lead author Sarah Dobner, the study reveals that vascular aging varies by tissue, showing increased inflammatory markers, altered nuclear YAP protein localization, and reduced vessel-sprouting gene activity in older venous cells.

Creation and scope of the atlas

• ▪The Human Aging Endothelial Cell Atlas analyzed single-cell data from 34 existing studies covering over 375,000 cells across 290 healthy samples from 12 human tissues.
• ▪The Nature Aging study on endothelial cell aging was led by first author Sarah Dobner, a Ph.D. student in Laura de Rooij's research group.
• ▪Researchers led by Laura de Rooij at the CeMM Research Center created the Human Aging Endothelial Cell Atlas to map gene activity changes in aging blood vessels.
• ▪The Human Aging Endothelial Cell Atlas study evaluated nondiseased tissues across different age groups rather than following individual donors over time.

Gene activity changes in vessel aging

• ▪Single-cell data from multiple healthy human tissues revealed age-related increases in endothelial cell gene activity associated with inflammation and cellular senescence.
• ▪The Human Aging Endothelial Cell Atlas demonstrated that endothelial cell aging is non-uniform and varies substantially across different organs and tissues in the human body.
• ▪Researchers identified a group of age-related genes associated with p21, a protein capable of slowing or stopping cellular division.
• ▪The Human Aging Endothelial Cell Atlas identified age-related gene changes involved in mechanotransduction, the process by which endothelial cells sense physical blood flow forces.

Mechanosensing and cellular senescence mechanisms

• ▪Comparisons with laboratory-grown endothelial cells and mouse models of accelerated aging linked p21-associated genes to stress responses and cellular senescence.
• ▪Human skin experiments showed that the mechanosensing protein YAP appeared more frequently inside the nuclei of endothelial cells from older donors.

Endothelial function in vessel formation and health

• ▪Reduced activity in several genes responsible for blood vessel formation and sprouting in older venous endothelial cells suggests a potential decline in vascular self-renewal capacity with advancing age.
• ▪Endothelial cells form the inner lining of blood vessels, regulating blood flow, tissue transport, brain protection, and kidney filtration functions.
• ▪Endothelial cells lining human veins can give rise to sprouts that develop into new blood vessels, playing an important role in vascular renewal.
• ▪As people grow older, endothelial cells can become dysfunctional, increasing susceptibility to cardiovascular disease and its associated mortality.