07 June 2019

Age mosaicism

Long-livers found in mouse liver

Scientists were able to do this thanks to a new technique by which they measured the age of cells of different types

Polina Loseva, "The Attic"

One of the reasons for the aging of the body is the lack of dividing cells. Tissues with a low rate of renewal, for example, nervous tissue, suffer especially strongly from it. Each neuron is unique, it is extremely difficult to replace it, so nerve cells carry their service throughout the life of the body. American scientists have developed a method to estimate the age of individual cells and even proteins. In addition to neurons, they found many more cells that have not been renewed since the very beginning of life – in blood vessels, liver and pancreas.

It is believed that multicellular animals owe their short life to complex tissues that are slowly being renewed. This is, for example, bone, which consists almost entirely of intercellular matter, or the brain, whose cells perform unique functions and are virtually irreplaceable. Therefore, neurons almost do not divide after birth and, consequently, each cell lives as many years as the body as a whole.

American scientists measured the age of individual cells using nitrogen isotopes. To do this, they fed female mice with food containing a heavy version of nitrogen, 15 N. A month after the start of feeding, they were crossed with males, and then continued to give them the isotope throughout pregnancy.

As a result, heavy nitrogen "enriched" the born cubs, becoming part of their proteins and DNA. During the first month of life, scientists continued to feed the mice with heavy nitrogen, and then changed it to the usual isotope, 14 N. Cells and proteins that have not been renewed since birth have retained a heavy isotope, and new molecules have received light nitrogen atoms at their disposal. The researchers then used mass spectrometry to measure the ratio of 15 N to 14 N in individual cells to estimate the age of individual tissue components.

As a reference, they took nerve cells from the motor area of the cerebral cortex, about which it is known for sure that they practically do not reproduce. The ratio of isotopes in them was 5-10 times higher than in a conventional culture of dividing cells. Therefore, scientists have proposed to consider "old" cells in which the heavy isotope is at least 5.5 times more than the "norm".

After examining the brain tissue in detail, they found that not only neurons, but also endothelial cells (lining the vessel wall), surrounding fibroblasts (elements of connective tissue) and oligodendrocytes (cells that isolate neurons from the environment) were "old" in it. But if for oligodendrocytes and in previous works, scientists have given evidence of a long life, then endothelial cells have always been considered actively renewing. According to new data, at least in the brain, this is not the case.

Then the researchers decided to look for long-lived cells in other tissues of the mouse body. The next object of their attention was the liver, known for its ability to regenerate. It turned out that most of the liver cells are as old as the rest of the animal's body. But the walls of the liver vessels are actively updated (unlike the brain) and probably maintain their long-living neighbors in a viable state. And in the pancreas, which scientists tested after the liver, the situation was completely different: the whole gland was a mixture of cells of different ages.

The authors of the article propose to revise the prevailing views on the aging of tissues in the body. It has long been known that tissues are a kind of genetic mosaic, since each cell carries a unique set of mutations acquired during life. Now we have to admit that the fabrics are mosaic in terms of age. The usual idea of renewing, "young", tissues, as opposed to non-dividing, "old", will have to be replaced with a new one: tissue as a combination of heterogeneous cells, the ratio and interaction of which can move age-related changes in the work of organs.

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