Scientists have uncovered the role of death protein in the aging of blood stem cells

Scientists have discovered that the MLKL protein, known as a mediator of cell death, covertly accelerates the aging of hematopoietic stem cells by damaging their mitochondria rather than destroying the cells themselves. The results of the work were published by Nature Communications on April 6.

"We found an unexpected phenomenon in the hematopoietic stem cells of mice with the MLKL gene disabled: age—related functional changes were significantly weakened, despite the fact that we did not observe any difference in cell death. This prompted us to investigate whether this pathway is capable of causing functional changes unrelated to cell death," said the head of the study, Dr. Masayuki Yamashita.

Experiments on genetically modified mice have shown that under stressful conditions — inflammation, replicative and oncogenic stress — the MLKL protein temporarily moved to the mitochondria and caused damage to them. The potential difference of the membrane decreased, the structure of mitochondria was disrupted, and energy production decreased. This, rather than cell death, triggered the typical signs of aging: hematopoietic stem cells were less self-renewing, produced fewer lymphoid cells, and shifted towards excessive production of myeloid cells, which weakens the body's immune response.

When the MLKL gene was disabled, the stem cells retained their ability to regenerate, formed a healthier immune cell composition, accumulated less DNA damage, and maintained normal mitochondrial function. It is noteworthy that the improvements occurred without significant changes in gene expression or chromatin availability — that is, MLKL affects aging primarily at the level of cellular structures, rather than through DNA regulation.

According to Dr. Yamashita, in the future, the study may lead to the creation of therapies that preserve the function of hematopoietic stem cells in patients after chemotherapy, radiation or transplantation, as well as open a new class of mitochondrial protective drugs.

Hematopoietic stem cells are responsible for the production of all types of blood cells. With age, they gradually lose their effectiveness: they are worse updated, disrupt the balance of immune cells and less strongly support the protective functions of the body. Until now, scientists have not been able to fully explain how different types of cellular stress combine and disrupt the functioning of these cells. The discovery of the role of MLKL as a common link between stress and mitochondrial damage offers a new approach to slowing the age-related decline of the immune system.

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Nutritionist Roman Pristansky warned on March 16 about the dangers of reducing the amount of fat during a diet. He stressed that fats are the most energy—intensive substrate of the body, which performs an important structural function, participates in the production of hormones and provides the body with energy. He called the optimal norm from 0.5 to 1 g per 1 kg of body weight per day. The same principle, according to Pristansky, applies to protein.