And it's hard to breathe
Old T-lymphocytes were found to have breathing problems
Ekaterina Kharybina, Vera Mukhina, N+1
With age, the protective ability of the immune system decreases and this is largely due to the fact that the number and diversity of T-lymphocytes decreases, and existing cells do not respond to infections as quickly as in youth. Analyzing the metabolism of immune cells in mice, scientists found that the cause of the decrease in the activity of T-lymphocytes may be a metabolic disorder in the mitochondria. The results of the study are published in the journal Proceedings of the National Academy of Sciences (Ron-Harel et al., Defective respiration and one-carbon metabolism contribute to impacted naïve T cell activation in aged mice).
When an infection enters the body, the lymphocytes that recognize it awaken, begin to actively divide and destroy pathogenic cells. Not yet specialized T-lymphocytes practically cease to be produced by the thymus after puberty and age together with the body, so that with age their number decreases, and they themselves become "heavy on the rise" and multiply worse. Therefore, infectious diseases are more severe in older people, and the effectiveness of vaccination is lower than in young people. The biochemical causes of aging of immune cells are poorly understood.
Awakening requires serious energy costs from T-lymphocytes. In addition, the cell needs building materials for division, so its metabolic rate increases. At the same time, the load on the mitochondria – the main energy stations of the cell – increases, so the researchers suspected that the aging of lymphocytes may be associated with a change in their activity. Previously, it was shown that single-carbon metabolism plays an important role in the activation of T-lymphocytes. This is a sequence of reactions in mitochondria, during which special enzymes transfer single-carbon groups from one molecule to another. Cells use the products of these reactions for the synthesis of nucleotides and amino acids, as well as for energy production.
A group of scientists led by Noga Ron-Harel from Harvard suggested that disruption of this pathway reduces the efficiency of T-lymphocytes in aging. To test this hypothesis, the researchers took not yet specialized T-lymphocytes from young and old mice and compared the process of their activation. Mice aged about two months were considered young, and 20-22 months were considered old (the average life time of mice in captivity is about two years). Compared to young cells, old cells were less activated in response to stimulation, they divided less and produced fewer activation indicator substances.
Activity of CD25 and CD69 genes, characteristic of early "awakening" of T-lymphocytes. It can be seen that it is relatively high in 86% of young cells (left), whereas among the lymphocytes of old mice (right), the proportion of such cells is less and amounts to 55%.
The authors also evaluated the ability of mitochondria of cells to breathe, performed mass spectrometry of metabolites and proteomic analysis of mitochondrial proteins. The mitochondria of old cells were smaller and produced little energy, which led to a relatively low level of a number of synthesized substances, such as nitrogenous bases that make up DNA and RNA. Scientists also observed a shortage of enzymes of single-carbon metabolism.
It turned out that if you try to "save" old T-lymphocytes and add substances synthesized during this pathway to them from the outside, then the effectiveness of their activation outside the body will increase. The researchers plan to test the activity of cells "fed" in this way in old mice. The data obtained can be used to develop ways to stimulate the immune response to infections in the elderly.
Recently, immunotherapy of cancer tumors has been gaining momentum. This fall, scientists who have learned to "unlock" the immune system to fight cancer have received the Nobel Prize in Physiology or Medicine.
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