The hematopoietic system can be rejuvenated
Researchers at the Cincinnati Children's Clinic Medical Center (USA) and Ulm Medical University (Germany), working under the guidance of Dr. Hartmut Geiger, managed to achieve functional rejuvenation of hematopoietic stem cells. Perhaps in the future this approach will help to combat a number of problems associated with old age.
Hematopoietic or hematopoietic stem cells are part of the bone marrow and give rise to all types of blood cells and the immune system: erythrocytes, leukocytes and platelets. As the body ages, the number of these cells increases, but the effectiveness of their proliferation and differentiation into mature cells decreases. This increases the predisposition of elderly people to infectious diseases and malignant diseases of the hematopoiesis system.
Earlier studies have shown that Cdc42 protein, which regulates the work of signaling mechanisms in cells, is characterized by increased expression in cells of various tissues of aging mice. Increased expression of this protein was also detected in the leukocytes of elderly people.
This prompted scientists to study Cdc42 in more detail. Experiments on mice have shown that increasing its activity using genetic methods induces premature aging of hematopoietic stem cells. Such aging cells lose their structural organization and polarity, which leads to a decrease in their functional efficiency.
At the same time, a decrease in Cdc42 activity in aging mouse hematopoietic cells using a selectively acting pharmacological inhibitor CASIN improved their condition and restored functionality to levels characteristic of young cells.
To make sure that the cells really got younger, the researchers used a method of so-called competing transplantation. This consisted in the isolation of hematopoietic stem cells from the bone marrow of young (2-4 months) and old (20-26 months) mice and their subsequent cultivation in laboratory conditions. During cultivation, the cells of old animals were subjected to a "rejuvenation" procedure. Subsequently, two populations of cells were transplanted to mice with a previously destroyed hematopoiesis system and the processes of bone marrow repopulation and restoration of hematopoiesis were observed. These observations confirmed that the functional parameters of the rejuvenated cells do not differ from the cells isolated from the bone marrow of young animals.
The images show the difference between the fluorescent structural and functional components of young and aging hematopoietic stem cells. In young cells, proteins are grouped into distinct structures, whereas in aging cells they are disorganized and scattered throughout the cell volume.
The authors plan to test the Cdc42 CASIN inhibitor on experimental models in vivo and analyze its effect on the condition of various tissues, in particular, on the level of erythrocyte production, animal endurance and the effectiveness of their immune responses. They will also analyze the reaction of human hematopoietic cells to changes in the expression level of Cdc42 in the laboratory.
Article by Maria Carolina Florian et al. Cdc42 Activity Regulates Hematopoietic Stem Cell Aging and Rejuvenation published in the journal Cell Stem Cell.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Cincinnati Children's Hospital Medical Center:
Aged Hematopoietic Stem Cells Rejuvenated to be Functionally Younger.
04.05.2012