As we age, our hematopoietic and immune systems gradually decline, so the elderly are more susceptible to diseases such as hematopoietic failure, infection, and tumors. Aging significantly reduces the ability of hematopoietic stem cells to generate new blood cells and disrupts the balance of immune cell production. These phenomena are directly related to their metabolic changes. Studies have found that defects in mitochondrial autophagy in hematopoietic stem cells may be one of the reasons that affect stem cells. Mitochondria are key organelles in cells that are responsible for energy metabolism, and abnormalities in their function can lead to cell aging and death.
A recent study led by Nicola Vannini, head of the Immunoaging and Stem Cell Metabolism Group at the Department of Oncology at the University of Lausanne in Switzerland, found that Urolithin A, also known as urolithin A, which has mitochondrial regulatory function, can reverse this aging process. The research paper was published in the journal Nature Aging.
Urolithin A is a secondary metabolite produced by the metabolism of natural polyphenolic compound ellagitannins by intestinal microorganisms. It is believed to have anti-inflammatory, anti-aging, antioxidant, and mitochondrial autophagy-inducing effects. It can cross the blood-brain barrier and inhibit PI3K/Akt/mTOR signaling.
Vannini and his colleagues cultured "aged" hematopoietic stem cells in the presence of urolithin A and found that urolithin A can correct the abnormal accumulation of mitochondria in hematopoietic stem cells and promote mitochondrial circulation, thereby significantly restoring the energy metabolism and function of "aged" hematopoietic stem cells-normal hematopoietic ability. This makes it possible to solve the problem of age-related weakening of the immune system caused by the "aging" of hematopoietic stem cells over time.
To assess whether this improvement in hematopoiesis would also lead to improved immune system function, the researchers infected old mice that had been treated with urolithin A for eight weeks with lymphocytic choriomeningitis. Virus-specific immune responses assessed eight days after infection showed that mice treated with urolithin A were better able to control the virus, with an enhanced CD8+ T cell response that could be directly attributed to the restoration of hematopoietic stem cell function. Overall, these experiments suggest that urolithin A can enhance the hematopoietic and immune systems of old mice.
Their studies also showed that a diet supplemented with urolithin A enhanced hematopoietic stem cell function, restored lymphocytes, corrected the imbalance between lymphocytes and bone marrow immune cells that occurs with aging, and improved the immune response to viral infection in old mice. The results suggest that promoting mitochondrial recycling can reverse the aging phenotype of the hematopoietic and immune systems.
"This is the first time that it has been shown that replacing defective mitochondria with healthy ones can reverse the aging of hematopoietic stem cells," Vannini said. "This was tested in 'aged' human hematopoietic stem cells and it was demonstrated that their function was significantly enhanced. Therefore, I expect it will have a similar effect on the human immune system."
The findings of this study provide a new direction for the development of anti-aging treatments in the future. In addition to reversing the aging of the hematopoietic system and immune system, urolithin A may also have anti-aging effects on other organs and cell types. In the future, researchers will continue to study the mechanism of action and application range of urolithin A in depth to provide more scientific basis for human anti-aging research.