Blood stem cells in the bone marrow are responsible for the production of blood cells. Image: allinonemovie from Pixabay
The blood stem cell reservoir becomes less diverse and less effective with increasing age, raising susceptibility to disease.
British researchers have used a new analytical method to discover that as people age, the diversity of the blood stem cell reservoir declines. This reduction in diversity contributes to increased chronic inflammation and susceptibility to disease (Nature, 21 May).
Blood stem cells in the bone marrow are responsible for producing blood cells, including immune cells. Blood stem cells can specialise through cell division into a clone. Young people have a large diversity of clones, which means their blood also consists of a wide variety of blood cells that can respond rapidly to stressors such as disease or environmental changes. First author Martina Braun writes in an email: ‘Until now, we were unable to compare the origin of different blood cells reliably, because existing methods rely on genetic manipulation. This is not ethically permissible with human subjects.’
Barcode
The British researchers therefore developed the analytical method EPI-Clone, enabling them to trace the clonal origin of individual blood cells. EPI-Clone scans the DNA methylation signature of individual cells – described by the researchers as a kind of barcode. This signature is preserved during cell division, making it possible to identify the shared ancestral clone of the cells, even when those cells have since differentiated to perform different functions.
Inevitable
Using the method, the researchers analysed 230,358 blood cells from humans and mice. They found that in older mice, 70 per cent of blood stem cells could be traced back to just a few dozen clones. In younger mice, this figure was 50 per cent. The same pattern was observed in humans. The study concludes that the ageing process becomes visible around the age of 50. Braun: ‘In 60-year-olds, the change was inevitable.’
Using the method, the researchers analysed 230,358 blood cells from humans and mice
Some dominant clones produce more myeloid cells, which are linked to chronic inflammation. This comes at the expense of lymphocyte production, which acts against acute infections. Earlier research has already established that the change also increases the risk of heart disease and leukaemia. Braun: ‘We found that some of the affected clones carried gene mutations, but some did not. The deterioration in blood production is therefore not caused solely by gene mutations, but by age itself.’ With their new technique, the researchers have substantially reduced the cost of producing a ‘clone map’ – an overview of an individual’s blood production system – Braun writes. In the future, they aim to reduce costs further in order to deploy the technique in hospitals.