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Young Bone Marrow Transplants Offers Hope for Alzheimer’s Research

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Mice that received bone marrow transplants from younger mice as part of a recent study had lower levels of many signs of brain aging. The researchers decided to explore this avenue because previous studies had shown that, as people age, the diversity of their hematopoietic — blood cell-generating — stem cells drop, through a mechanism known as clonal hematopoiesis.

Stem cells with mutations that drive proliferation dominate the stem cell population, thus reducing its overall diversity. In this instance, the researchers looked at the effect of bone marrow transplants on the brain and Alzheimer’s disease markers. To investigate the relationship between the age of hematopoietic stem cells and brain aging, and whether or not a bone marrow transplant can restore them, researchers used 9- and 2-month-old mice that had been genetically engineered to model Alzheimer’s disease.

They made two groups of 9-month-old mice and gave one group bone marrow transplants from 2-month-old mice, and a control group bone marrow transplants from other, 9-month-old mice. 

They first compared the expression of genes in older and younger mice and identified a number of age-related genes that were either up or downregulated in the older mice. Up-regulated ageing pathways identified in the older mice were commonly associated with mitochondrial function, and down-regulated aging pathways were commonly associated with epigenetic regulation and immune processes. Researchers also compared the expression of the top 45 Alzheimer’s disease risk genes in the different types of immune cell. 

They found that the top 10 Alzheimer’s disease risk genes were differentially expressed in a type of white blood cell called monocytes in older mice, and young bone marrow transplants reversed these expression changes. The young bone marrow transplant is improving the function of the immune system both systemically and in the brain.

The use of young, allogeneic donors for proposed interventions on ageing such as heterochronic parabiosis or bone marrow transplants, would be fraught with ethical concerns regarding equity and exploitation, conjuring up dystopian future images of billionaire ‘vampires’ obtaining young blood or bone marrow to keep themselves young. One way to avoid this would be to use heterochronic autologous transplants, that is, taking your blood or bone marrow from an earlier age and then transplanting it back into yourself, which might show similar effects.

However, if research can identify the specific aspects of these transplants that affect the aging process — for example, serum blood proteins seem to be important in heterochronic parabiosis — then the benefits might be obtained without a transplant at all. In both of these scenarios, the risk of exploitation would be diminished, though there would still be important ethical concerns regarding access to treatment.