In the human body, the production of blood cells changes with age, as a result of the mutations that affect blood stem cells over the years, altering their proliferation and sometimes causing tumors. This is demonstrated by a genetic study conducted on almost 400 Sardinians who regularly donated blood to science as part of the great SardiNIA research project. The results, useful for the fight against cancer and aging diseases, are published in Nature from the Wellcome Sanger Institute with the Cambridge Stem Cell Institute and the European Institute of Bioinformatics (EBI) which is part of the European Molecular Biology Laboratory (EMBL). For Italy, researchers from the Institute of Genetic and Biomedical Research of the National Research Council (Irgb-Cnr) collaborated.
All human cells accumulate DNA mutations over time, some of which favor proliferation. This phenomenon is common in blood stem cells and results in the growth of populations of cells that carry the same mutations and are referred to as ‘clones’. This process of ‘clonal hematopoiesis’ becomes ubiquitous with age and promotes the development of blood cancers and other diseases related to aging. To better study it, the researchers traced the evolution of nearly 700 clones of blood cells isolated from 385 people over 55 who, as part of the SardiNIA study, donated blood regularly over a period of time up to at 16 years old. The DNA sequencing extracted from the blood samples shows that 92% of the clones grew at an exponential rate that remained stable over the study period. The nature of the mutated gene in each clone determines the growth rate. After ‘photographing’ the behavior of the clones in old age, the researchers used mathematical models to reconstruct their growth throughout human life. They found that the behavior of the clones changes dramatically with age depending on the mutated gene.
Clones with mutations in the DNMT3A gene, for example, expand rapidly in young people and decelerate in old age; clones with mutations in the TET2 gene, on the other hand, appear and grow uniformly over a lifetime; finally, clones with U2AF1 and SRSF2 mutations expand in old age with one of the fastest growth rates. These different age-related behaviors mirror the frequency with which different types of blood cancers arise and reveal that mutations associated with rapid clone growth are more likely to cause malignant tumors.
“Understanding why some mutations prevail in young people and others in old age could help us find ways to maintain the health and diversity of our blood cells,” comments Margarete Fabre, a researcher at the Wellcome Sanger Institute and the University of Cambridge.
Equally interesting results were produced by a second study, always published in Nature from the Wellcome Sanger Institute and the Wellcome-MRC Cambridge Stem Cell Institute. The researchers sequenced the entire genome of more than 3,000 blood stem cells from 10 individuals of all ages. From the analysis it emerged that under the age of 65 the production of blood cells is the work of tens of thousands of stem cells, while after the age of 70 over half of the blood is produced by a handful of stem cell clones: this greatly reduces genetic variability. of cells and promotes the onset of diseases.
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