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Study reveals what happens to blood cell production during the ageing process, which could help identify new therapeutic targets.

Inside blood vessel red and white blood cells 3D rendering

A study published in Nature Communications by the Nerlov Group sheds light on what happens to blood cell production during the ageing process. As people age, they have a declining immune response and frequently suffer from anaemia. Identifying new therapeutic targets may eventually make it possible to revert this process, boosting the immune response and avoiding anaemia.

As organisms age, the effectiveness of replenishing blood cells decreases, particular for red blood cells and those white blood cells (lymphocytes) that produce antibodies and kill virus-infected cells. This leads to higher rates of anaemia (because of fewer red blood cells), as well as too few infection-fighting white blood cells in older people. Bone marrow stem cells which give rise to all blood cell types are affected by many factors, including cues coming from the ‘microenvironment’ around the cell.

The Nerlov group set out to detect changes during ageing in the stromal cells that make up the bone marrow microenvironment. They found that both the IL-6 and TGFb signalling pathways were upregulated across multiple stromal cell types.

In particular, the researchers found that in aged mice inhibition of TGFb signalling increased the ability of aged bone marrow stem cells to generate lymphocytes. However, the age-associated decrease in red blood cell production was not due to stem cell ageing, but instead to the effect of IL-6 and TGFb signalling on the precursor cells that generate the red blood cells: by inhibiting both IL-6 and TGFb signalling both the number and function of red blood cell precursors was restored.

The computational method that the researchers used (which capitalised the MRC WIMM’s state-of-the-art genomics platforms) to uncover these processes is also novel, and can potentially be used to study both developmental and pathological processes.

Dr Simona Valletta, first author of the study said: “This important result highlights a crucial role played by the aged microenvironment within organisms in the inhibition of the generation of red blood cells, with IL-6 identified as a potential target for therapeutic intervention. Our research, understanding the underlying causes of the age-associated decrease in red and white blood cell production, and identifying pharmacological strategies to counteract them, provides significant insights for the development of new targeted treatments. This represents an important step towards improving the health of the ageing population.” 

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