Published atlas of 375 thousand cells compares age-related vascular changes across 12 human tissues

Published atlas of 375 thousand cells compares age-related vascular changes across 12 human tissues

A study published on October 23 in Nature Aging describes 375 829 cells from the inner lining of vessels, drawn from 290 samples of 12 healthy human tissues. The authors compared age-related changes across organs and parts of the vascular system.

The endothelium forms the inner lining of vessels. It allows substances to pass between blood and tissues and contributes to blood clotting and the growth of new vessels. Earlier maps generally focused on individual organs; this atlas looks for recurring age-related changes throughout the vascular network.

The authors combined 34 public datasets in which RNA measurements indicate which genes are active in individual cells or their nuclei. They used the donor sample as the unit of comparison, comparing biological samples and assessing differences between age groups within each tissue. Repeating the analyses with different age cutoffs, subsets of samples and a combined assessment across datasets confirmed the observed shifts.

Samples from older age groups showed increased activity in sets of genes associated with inflammation and cellular senescence, alongside reduced activity in genes involved in angiogenesis, the growth of new vessels. These changes were most pronounced in the venous endothelium. The atlas shows both a shared pattern of age-related changes and differences among arteries, capillaries, veins and lymphatic vessels.

In the skin, age-related changes affected genes associated with the extracellular matrix, the supporting material around cells that transmits mechanical signals to them. RNA measurements in tissue sections and protein staining showed that YAP was more often located in the nuclei of endothelial cells in the older group. YAP is a protein through which cells adjust gene activity in response to the properties of this supporting material.

The authors used p21, a protein that slows cell division, as a starting point to search for related changes. Increasing expression of the gene MAFF in young endothelial cells raised p21 levels and increased the activity of an enzyme associated with cellular senescence.

The publicly available data and code allow researchers to examine which age-related changes are specific to a tissue or a particular part of the vascular system.