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Longevity Briefs: Restoring Balance To An Ageing Immune System

Posted on 2 April 2024

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Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

As we age, the ability of our immune system to fight off invading pathogens declines. One of the reasons for this is a disturbance in the balance between two families of blood cells. Stem cells in the bone marrow (haematopoietic stem cells) can produce cells from the lymphoid family, which includes T and B white blood cells that mount a precise immune response towards a specific pathogen. Alternatively they can produce cells from the myeloid family, which includes red blood cells as well as less specific, more inflammatory white blood cells. As we age, bone marrow stem cells start to produce more cells from the myeloid family and fewer cells from the lymphoid family. This is a bad thing because it leads to increasing levels of inflammation (due to the more inflammatory white cells) and reduced ability to respond to new pathogens (due to the depletion of T and B cells).

A diagram showing the myeloid and lymphoid lineages.
By A. Rad and Mikael Häggström, M.D.
Image: Hematopoiesis (human) diagram.png by A. Rad, CC BY-SA 3.0,

The discovery:

In this study published in the journal Nature, researchers found that they could restore the balance of immune cell types in aged mice simply by depleting the ‘biased’ myeloid-favouring stem cells. They found that the biased stem cells expressed certain proteins on their surface that were absent from the more balanced stem cells. They were then able to produce antibodies to target these proteins, thereby destroying the myeloid-favouring stem cells while leaving the balanced cells untouched. When these antibodies were given to 18-24 month-old mice (lab mice live for about 28 months), the balance between lymphoid and myeloid cells was significantly improved. Treated mice had significantly lower levels of inflammatory molecules and more naive T and B cells (these are ‘blank slate’ immune cells with the potential to respond to new pathogens that haven’t been encountered by the immune system before). These changes lasted at least 16 weeks after a single treatment.

Most importantly of all, these changes in immune cell balance translated to an improved immune response. Old and young mice were injected with a non disease-causing virus (essentially a vaccine), and as expected, the young mice mounted a much stronger immune response when compared to the older mice. However, old mice whose myeloid-biased stem cells had been depleted mounted a significantly stronger immune response than the untreated mice, suggesting a more competent immune system.

The implications:

It seems as though simply destroying the myeloid-biased stem cells allows other stem cells to rebalance the whole stem cell population, leading to reduced inflammation and better immune function. The same proteins targeted by antibodies in this study were actually confirmed to be present on a subset of human hematopoietic stem cells, so there may be an opportunity to apply this treatment to humans eventually. Addressing the imbalance of immune cell types in old age could have many benefits beyond simply defending against disease. It should improve responsiveness to vaccination while protecting against cancer, autoimmune disease and senescent cells. It would also reduce age related inflammation, thereby (hopefully) protecting against many other age related diseases like Alzheimer’s and diabetes.

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    Title image by Elena Mozhvilo, Upslash

    Depleting myeloid-biased haematopoietic stem cells rejuvenates aged immunity

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