Scientists have mapped the aging of blood vessels

With age, changes occur in the body that affect not only individual organs, but also the circulatory system. The inner lining of blood vessels consists of special cells that regulate blood flow, metabolism with surrounding tissues, and damage response. However, the mechanisms of aging of these cells are still poorly understood. About what changes occur in blood vessels with age and why they can affect their ability to recover — in the material of Izvestia.

How scientists have studied vascular aging

An international team of researchers led by Laura de Roy from the CeMM Center for Molecular Medicine at the Austrian Academy of Sciences has created the first comprehensive map of human endothelial cell aging. These cells form the inner lining of blood vessels and are involved in regulating blood flow, controlling metabolism between blood and tissues, and repairing damage.

For the analysis, the researchers combined data from 34 previously published studies. In total, they studied the activity of genes in more than 375 thousand cells obtained from 290 samples of 12 types of human tissues. The work was published in the journal Nature Aging.

The researchers focused on tissues that were classified as healthy or undiagnosed. This allowed us to look for molecular changes related specifically to aging, rather than primarily to diseases that have already developed.

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Why can blood vessels lose their ability to repair

One of the important observations was changes in the cells lining the veins. Such cells can participate in the formation of new vascular branches necessary for the renewal of the blood network. However, in older people, the researchers found a decrease in the activity of several genes associated with the formation of blood vessels.

This may partly explain why the vascular system's ability to renew itself weakens with age. At the same time, scientists did not directly measure the ability of blood vessels to recover, so the revealed relationship cannot be considered direct evidence of a deterioration in this process. In several types of tissues, the researchers also found increased activity of genes associated with inflammation and cellular aging. In this state, the cells stop dividing, but they can affect the surrounding tissues.

How cells react to environmental changes

Endothelial cells constantly perceive mechanical effects related to the movement of blood and the properties of surrounding tissues. They then convert these signals into biological responses. The analysis showed that the activity of the genes involved in this process changes with age.

Additional experiments with human skin tissues revealed another feature: in elderly donors, the YAP protein was more often found inside the nuclei of endothelial cells. It helps cells respond to mechanical stress. However, the significance of this change is not yet clear. The researchers will have to find out whether an increase in YAP activity helps cells adapt to age-related changes or, on the contrary, contributes to the deterioration of vascular function.

The scientists also studied a group of genes associated with the p21 protein, which is able to slow down or stop cell division. A comparison of the results with data from laboratory experiments and models of accelerated aging in mice confirmed the association of these genes with cellular aging. At the same time, they are involved both in the stress response and in the formation of blood vessels, so their activity cannot unambiguously determine which cells have finally lost their ability to divide.

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Why do blood vessels age differently?

The study showed that age-related changes in endothelial cells vary in different parts of the vascular system. As noted by the first author of the work, Sarah Dobner, the study of cells from various tissues revealed patterns that could have gone unnoticed when analyzing individual organs or cell types.

The created map allows researchers to study the molecular changes in the vessels of different organs. Along with the work, an interactive resource was also presented, which should help specialists explore the data obtained and determine directions for future experiments.

What questions remain open?

The study has limitations. Scientists compared data from people of different ages, but did not observe changes in the body of the same participants throughout their lives. In addition, information about the lifestyle of donors and their medical history was incomplete, which limits the interpretation of the results.

Therefore, it is not yet possible to unambiguously determine which of the detected changes directly lead to a deterioration in vascular function, and which represent the adaptation of cells to changing conditions. As the head of the study, Laura de Roy, emphasized, the created map makes it possible to study the aging of blood vessels in different parts of the body, rather than considering all blood vessels as a single system with the same changes.

The authors hope that further study of these processes will help to better understand the mechanisms of age-related changes in the vascular system and identify promising areas for future research.