All organs in the human body age over time, and the process of producing blood cells from the bone marrow, hematopoiesis, is no exception. A recent study deciphers the mechanisms responsible for this aging and reveals the interest of a drug used in rheumatoid arthritis to counter this phenomenon. Work published in the scientific journal Nature Cell Biology.
From hematopoietic stem cells to blood cells
All blood cells, red blood cells, white blood cells and platelets, are produced from hematopoietic stem cells found in the bone marrow. Bone marrow is a spongy tissue, located in the center of the bones. Alongside hematopoietic stem cells, the bone marrow contains cells that produce various substances that contribute to the development and regulation of blood cell production.
Throughout our existence, hematopoietic stem cells produce blood cells, the lifespan of which remains relatively short, around 120 days for a red blood cell. But like the rest of the body’s functions, this hematopoietic function ages over the years. With age, the capacity of hematopoietic stem cells deteriorates and exposes the elderly to increased risks of anemia and weakening of the immune system (increased risk of infections and development of certain cancers). Although various studies have focused on the progressive alteration of the capacities of hematopoietic stem cells, few studies have been carried out on the other cells of the bone marrow.
Inflammation responsible for aging blood cell production
Recently, researchers conducted a study on mouse models. They observed that the bone marrow of old mice showed an altered cellular composition and impaired vascularization, compared to young mice. Moreover, some bone marrow cells from aged mice expressed markers of inflammation, including interleukin-1-beta. Interleukin-1-beta would participate in the aging phenomenon of the production of blood cells from hematopoietic stem cells.
However, interleukin-1-beta is also known to be involved in the development and evolution of certain chronic inflammatory pathologies, such as rheumatoid arthritis. One of the treatments for rheumatoid arthritis targets the interleukin-1 receptors, anakinra. Anakinra is able to neutralize the biological activity of interleukin-1-alpha and interleukin-1-beta by blocking their binding to cell receptors. This medicine is indicated as a second-line treatment in rheumatoid arthritis and helps limit the activity of the disease.
A drug capable of stopping the aging of the bone marrow?
The researchers then had the idea of treating the old mice with anakinra for two weeks. They then observed that the bone marrow of old mice regained functions comparable to those of young mice, in terms of blood cell production. Meanwhile, mice genetically deficient in interleukin-1 receptors did not exhibit the classic level of bone marrow aging of aged mice.
This new study has revealed the role of inflammation and in particular of interleukin-1, an inflammatory marker, in aging the production of blood cells from the bone marrow. Treatments targeting interleukin-1 proved capable in mice of countering this aging. An important discovery that might help better control of bone marrow aging in humans, and therefore reduce the risk of certain pathologies (infections, cancers) in the elderly. It remains to be seen whether the results observed in mice can be transposed to humans!
Estelle B., Doctor of Pharmacy
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