11 September 2020

Mosaic aging

In different tissues of the human body, telomeres shorten at different rates


A team of scientists led by researchers from the University of Chicago has determined the rate at which telomeres shorten in cells from different types of human tissues. Although it turned out that this rate may vary, scientists have concluded that a decrease in telomeres in blood cells can serve as a fairly accurate indicator for many other tissues.

Telomeres are sections of DNA at the ends of chromosomes that do not encode any signs. Telomeres are needed to protect the bulk of DNA from damage during cell division. Before cell division, a special DNA enzyme – polymerase – moves along the DNA chain and synthesizes its copy. But the polymerase is not able to start working from the very tip of the chromosome, so it begins to double it, slightly retreating from the edge. As a result, after each division, the chromosome decreases slightly. Telomeres are located at the ends of chromosomes so that coding regions are not affected by such a decrease. But gradually, after new and new cycles of division, telomeres will shrink more and more – this is the aging of the cell.

Telomere reduction is associated with aging and age–related diseases, but when studying these processes, telomeres are usually measured in cells that are easy to get from a patient, most often in blood cells. Until now, it remained unclear to what extent telomeres in blood cells can reflect the picture in other tissues of the body.

To study this issue, the authors of the work used the Genotype-Tissue Expression (GTEx) project, in which tissue samples are collected from a large number of people. In total, they analyzed more than 6,000 samples of 23 different tissues obtained from about a thousand people. They found that of these 23 tissues in 15, telomere length shows a clear positive correlation with telomere length in whole blood cells, which confirms the use of blood cells as an indicator of telomere length in hard-to-reach tissues such as brain and kidney tissues.

Along the way, scientists tested several previously put forward theories about the length of telomeres in various special cases. Some of them have been confirmed, such as longer telomeres in people of African descent. Others are not, for example, the assumption of a longer telomere length in women. The message about shorter telomeres in smokers was only partially confirmed, this is indeed observed, but only in some types of tissues. These results will help to understand how the length of telomeres is genetically determined, as well as how lifestyle, environmental influences or epigenetic changes during a person's life can affect it.

The results of the study are published in the journal Science (Demanelis et al., Determinants of telomere length across human tissues).

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