Researchers have achieved a rejuvenation of the immune system in aging mice by reducing abnormal stem cells within their bodies. This technique bolstered the response of elderly rodents to viral infections and reduced signs of inflammation. The findings were published in Nature on March 27th.
Blood Stem Cells (Artificially Colored)
Image Source: Science Photo Library
Researchers have manipulated aging mice by treating them with antibodies to reduce the population of stem cells capable of generating various other cell types, including cells that cause inflammation. Excessive inflammation can wreak havoc on the body, and these pro-inflammatory stem cells gradually become dominant in the aging mice and human body.
While it will take several years for this method to be tested in humans, there are many similarities between mice and humans in fields such as stem cell biology.
For decades, one of the corresponding authors, Irv Weissman's team at Stanford University, has been tracking the fate of blood stem cells. These stem cells can replenish red and white blood cells in the body.
In 2005, the Weissman team discovered changes in the number of blood stem cells as mice age. In young mice, two types of blood stem cells are in balance, each nurturing different branches of the immune system. The "adaptive" branch produces antibodies and T cells against specific pathogens, while the "innate" branch responds broadly to infections such as inflammation.
However, in older mice, this balance tilts towards pro-inflammatory innate immune cells. Similar changes have been reported in the blood stem cells of older humans, leading researchers to speculate that this could lead to a weakened ability to generate new antibody and T cell responses, explaining why older adults are more susceptible to severe infections from pathogens like the influenza virus and have weaker responses to vaccines compared to younger individuals.
If so, restoring the balance of blood stem cell numbers could rejuvenate the immune system. Researchers validated this by generating antibodies that bind to blood stem cells primarily producing innate immune cells. They then injected these antibodies into aging mice, hoping the immune system would destroy the stem cells bound to the antibodies.
The antibody therapy revitalized the immune system in mice, enhancing their response to vaccines and making them more resistant to viral infections compared to untreated elderly mice, while also lowering levels of inflammation-related proteins.
Robert Signer, a stem cell biologist at the University of California, San Diego, who was not involved in the study, stated that this demonstrates how different blood stem cells can influence the aging of the immune system.
Enca Montecino-Rodriguez, who studies white blood cell development at the David Geffen School of Medicine at the University of California, Los Angeles, suggested that antibody therapy may not only affect the dominant population of blood stem cells but also their environment or possibly clear other aging cells in the body or trigger an immune response, thereby affecting the mouse's response to vaccines and viruses.
Weissman's team is exploring a similar approach to rebalance aging human blood stem cells. However, even with sufficient funding and no unexpected setbacks, it will take at least three to five years before human testing can begin.
In the meantime, the research team will continue studying mice to understand more about the other effects of antibody therapy, such as whether it affects the incidence of cancer or inflammatory diseases.
Related Paper Information: https://doi.org/10.1038/s41586-024-07238-x
