Drop in diversity of blood stem cells leads to old-age health issues

Mutations which lead to the dominance of certain blood stem cells in the over 70s could be behind some of the health issues people experience in old age.

Changes in blood production in later life can lead to problems such as anaemia and lower immunity. The reasons for this have puzzled researchers, but a recent discovery that certain 'driver' mutations in blood stem cells accumulated over a lifetime can outcompete other groups of stem cells and reduce the overall diversity of blood stem cells present in old age.

'Our findings show that the diversity of blood stem cells is lost in older age due to positive selection of faster-growing clones with driver mutations. These clones 'outcompete' the slower-growing ones. In many cases this increased fitness at the stem cell level likely comes at a cost – their ability to produce functional mature blood cells is impaired, so explaining the observed age-related loss of function in the blood system.' said Emily Mitchell from Addenbrooke's Hospital and the Sanger Institute, Cambridge.

The Cambridge research team, working with the Wellcome Sanger Institute, investigated ageing by sequencing whole genomes of 3579 blood stem cells. The cells were taken from ten individuals aged 0–81, including two cord blood samples, and were analysed to see the relationship between mutations and ageing.

The analysis, published in Nature, determined blood production for the four adult individuals aged under 65 came from a population of 20,000 to 200,000 blood stem cells, all contributing evenly to blood production. But for the four participants aged over 70 there was a profound decline in the diversity of stem cells, with around 12–18 stem cells dominating blood production.

These active stem cells contained a specific driver mutation identified by the researchers, which causes these stem cells to grow faster. Faster-growing blood stem cells have health implications, such as association with blood cancers, and loss of diversity with lower response to infections.

'We've shown, for the first time, how steadily accumulating mutations throughout life lead to a catastrophic and inevitable change in blood cell populations after the age of 70. What is super exciting about this model is that it may well apply in other organ systems too. We see these selfish clones with driver mutations expanding with age in many other tissues of the body – we know this can increase cancer risk, but it could also be contributing to other functional changes associated with ageing.' added Dr Peter Campbell from the Wellcome Sanger Institute, Cambridge.

The loss of stem cell diversity may be a feature of ageing as other organ systems also experience similar accumulations of driver mutations as people age, authors said.