Blood stem cells acquire DNA mutations over time. These stem cells expand exponentially into clones which become commonly visible as a person nears 70, and which could give clues to why people can feel the effect of ageing, Dr Jyoti Nangalia, principal investigator at the Wellcome-MRC Cambridge Stem Cell Institute and Wellcome Sanger Institute, said at the Future of Medicine Summit of Happiest Health on 9 March.
“The accumulation of these clones of blood cells could be the reason for why we age,” said Dr Nangalia, who is a research group leader at the Wellcome Sanger Institute.
The human body has over 100,000 blood stem cells and each of these cells accumulate mutations in their DNA over time.
Blood cells with mutations that lead to an ‘advantage’ expand to produce clones of cells.  Some of these stem cell clones can expand exponentially over a lifetime, resulting in abrupt changes in a population of blood cells by the seventh decade of life, she said.
Nangalia and her team have worked on understanding how mutations in blood cells can lead to diseases such as leukaemia or blood cancer, and how this process influences ageing. Blood cells are produced in the bone marrow that host the stem cells, which then give rise to our different blood cells: white blood cells (leukocytes), red blood cells (erythrocytes), and platelets.
Blood is a life-sustaining component of our body, performing various functions such as circulating oxygen, nutrients and hormones and regulating body temperature. Due to their diverse roles, blood cells must be replenished frequently. The bone marrow is the epicentre of stem cells that generates new blood cells.
Some mutations turn out to provide a growth advantage to the cells, helping them multiply quickly; but at the same time, some of these errors result in disease conditions like blood cancer she added.
Dr Nangalia’s team focuses on understanding the genetic fingerprints of blood cancers and ageing. Dr Nangalia was the first to discover the association of CALR mutation with MPN during her PhD tenure. Her research group focuses on using sequencing technologies to understand precisely when blood cancers originate in people during their lifetime.
To trace back the steps, Dr Nangalia’s team develop sequencing technologies, bioinformatics and analysing software tools that map the mutation steps in a cancer’s history, to the exact interval during life when these disease-causing mutations occurred. For this, they use whole genome sequencing methods. Their exhaustive analysis reveals the blood cells’ phylogeny or ancestry and weeds out the mutation point. Their studies help identify mutations, the time and the growth rates of cancers as well as the trajectory of how blood ages over a human lifespan.
