24 November 2020

Epigenetics of aging

Biomarkers of aging were found in epigenetic labels of immune cells

Thanks to them, it is possible to accurately calculate the biological age of a person


Molecular biologists have discovered a previously unknown set of age-related changes in the structure of the DNA "wrapper" of some immune cells. With their help, you can accurately calculate the biological age of their owners. The results of the scientists' observations were published by the scientific journal Nature Aging (Shchukina et al., Enhanced epigenetic profiling of classical human monocytes reveals a specific signature of healthy aging in the DNA methylome).

"We know almost nothing about how the natural aging process affects the molecular program of immune cells. We tracked how the vital activity of monocytes changes with age (one of the types of immune cells, – approx. TASS) healthy people. Thanks to this, we have identified several sites in their genome, the epigenetic labels in which have changed greatly in one direction or the other," the researchers write.

As we age, the activity of many genes, as well as the concentration of important biological molecules, including various enzymes, signaling substances and antibodies, changes significantly. By tracking such changes, doctors can determine the biological age of a person and assess the rate of decrepitude of his body.

For example, a few years ago, biologists discovered that the concentration of one of the most important "helpers" of enzymes, nicotinamide-adenine dinucleotide (NAD), decreases very much as the body ages. This compound does not accelerate reactions by itself, but participates in the transfer of electrons from one molecule to another, helping cells extract energy from nutrients and produce new proteins and the most important "building blocks of life".

Russian and foreign scientists under the guidance of an associate professor at Washington University in St. Louis (USA) Maxim Artemov discovered another marker of aging. They studied how the behavior and work of monocytes – one of the most common types of immune cells - changes as their owners' bodies age.

For these experiments, scientists gathered a group of two dozen young and elderly men, whose average age was about 27 years and 64 years. The researchers received blood samples from them, extracted monocytes from them and comprehensively studied these cells. Analyzing the differences between them, biologists tracked not only changes in the concentration of enzymes and other important biomolecules, but also how the number and location of the so-called epigenetic labels changed.

Scientists call this the chemical modifications of either the DNA itself or the proteins with which it is associated. Thanks to epigenetic tags, organisms quickly adapt to new environmental conditions or flexibly change their behavior program in response to certain factors. For example, some plants use epigenetic labels in order to "remember" droughts, adapt to them and transmit this information to "descendants".

In the past, scientists believed that with age, the total number of such marks on the surface of DNA gradually decreases. Artemov and his colleagues found out that in some areas of the genome of immune cells, reverse processes can also occur. This idea was suggested to scientists by the fact that they found more than a thousand isolated regions in the DNA of volunteers, where the number of such tags increases or decreases unusually rapidly as they age.

These epigenetic changes significantly changed the work of genes. They stimulated the work of those parts of DNA where the number of tags decreased greatly with age, and suppressed those regions of the genome where their number grew rapidly. The totality of these labels, as shown by a comparison of their number in the cells of healthy volunteers, asthmatics and HIV carriers, very accurately reflects the biological age of a person and the rate at which he is aging.

Further observations showed that all changes in the epigenetic structure of these DNA regions were associated with two enzymes, MBD2 and MBD3. Previously, scientists did not associate them with the aging process. The study of these enzymes, scientists hope, will help to understand why they make changes in the structure of labels only in some regions of DNA and how these shifts affect the work of the immune system and the whole body as a whole.

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