The COVID pandemic has shown that elderly individuals are more susceptible to severe infectious diseases. This could result from changes in the production of the cells that protect against pathogens, immune cells, in our bone marrow. With age, our bone marrow produces less B and T immune cells, which fight foreign invaders, and produce more myeloid cells, which are responsible for creating a pro-inflammatory environment, leading to increased susceptibility to infectious disease. Many researchers have failed at elucidating the mechanism driving this shift, hampering the efforts to develop therapies to re-balance the immune system’s cell composition.
Researchers at Stanford University have overcome the roadblock by depleting the bone marrow stem cells responsible for preferentially generating myeloid cells in aged individuals. They achieve this by injecting in mice an antibody that binds to a molecule on the target cells’ surface and marks these cells for clearance by professional “cell-eating” cells. In aged mice, clearance of detrimental bone marrow stem cells by this antibody increases T and B cells levels and decreases myeloid cell levels as well as inflammation. Furthermore, upon injection of a virus, aged mice treated with the antibody therapy display better survival than untreated controls.
These findings suggest that this approach could boost the aged immune system’s response against pathogens but is limited by the fact that antibodies are injected intravenously. Elderly people might not be able to easily drive to the hospital for these injections or afford frequent treatment regimes. Surprisingly, the researchers observed that the therapy exerted long lasting effects. Two months post-treatment, the equivalent of 5 years in humans, the mice still exhibited a depressed myeloid blood population and inflammatory state. Hence, this therapy provides a user-centric solution capable of protecting our grandparents against common viruses such as COVID or influenza. However, further studies are warranted to prove the efficacy in human clinical trials.
This study was performed by postdoctoral fellow Jason B. Ross Lexiang Yu (PhD) in the lab of Irving Weissman, D.K. Ludwing Professor of Clinical Investigation in Cancer Research, Pathology and Developmental Biology at Stanford University.
Managing Correspondant: Allegra Carlotta Scarpa
Original Article: Depleting myeloid-biased haematopoietic stem cells rejuvenates aged immunity (Nature)
Press Article: Anti-ageing antibodies revive the immune system (Nature)
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