"Revitalizing the immune system with anti-ageing antibodies"

In a groundbreaking study published in Nature, researchers have discovered a new way to rejuvenate the immune system of aged mice using antibody therapy. The study found that depleting an expanding pool of aberrant stem cells in aged mice using antibody therapy can rebalance blood cell production, diminish age-associated inflammation and strengthen acquired immune responses.

As we age, our immune system becomes less efficient, making us more susceptible to infections and chronic diseases. One of the reasons for this decline is the aging of hematopoietic stem cells (HSCs), which are responsible for producing blood cells throughout our lives. With age, there is a substantial increase in the proportion of HSCs that are biased towards generating myeloid lineage cells, which include red blood cells, platelets, and cells of the innate immune system. This imbalance in blood cell production results in poor adaptive immune responses to infection and high levels of inflammation, making us more vulnerable to diseases.

To address this issue, the researchers took advantage of a key feature of myeloid-biased HSCs - a set of proteins expressed on their cell surface that makes them distinct from balanced HSCs. By mining transcriptional data sets, the authors identified three cell-surface proteins that could be used to identify, isolate, and target myeloid-biased HSCs in aged mice, and potentially in humans, with minimal off-target effects.

The researchers established an antibody conditioning protocol in which aged mice were treated with antibodies that targeted the cell-surface proteins that the authors had identified. They found that antibody conditioning preferentially depleted myeloid-biased HSCs, and that balanced HSCs were mostly spared. Furthermore, they found that a single course of antibody conditioning was durable, with the relative number of myeloid-biased HSCs remaining depressed for at least two months after treatment.

The study has significant implications for the development of new treatments for aging-related diseases. By rebalancing blood cell production and restoring adaptive immunity, depleting myeloid-biased HSCs in aged mice improved immunity in older adults, which could reduce infection-related morbidity and mortality.

Moreover, the study raises the possibility that targeting myeloid-biased HSCs could alleviate some of the detrimental effects of ageing by attenuating 'inflammageing' and reducing the incidence and severity of diverse age-related inflammatory diseases.

While the study offers a promising approach to rejuvenating the immune system of aged individuals, more research is needed to determine the safety and efficacy of this therapy in humans. However, the study provides hope for a future where we can delay the onset of aging-related diseases and improve the quality of life of older adults.

Source: <https://www.nature.com/articles/d41586-024-00680-x>