The loss of the Y chromosome, a mortality factor of cardiac origin

The Y is that small chromosome which, coupled with the X chromosome, gives an individual the male gender, while females feature the XX chromosome pair. The Y could also be responsible, by its fragility, for the greater mortality of cardiac origin observed in men. A study published on July 15 in the journal Science shows, for the first time, a causal link between the loss of the Y chromosome in certain blood cells, observed during aging, and a phenomenon of cardiac fibrosis.

“It’s a very good study, methodologically very complete, and I’m not saying this because I had the opportunity to co-sign works with one of its main authors, Lars Forsberg”welcomes Jean-Charles Lambert, from the Institut Pasteur Lille, who is also interested in this phenomenon of mosaic loss of the Y chromosome (known as “mLOY”, for Mosaic Loss of Chromosome Y), but in connection with the disease of Alzheimer’s.

Lars Forsberg (University of Uppsala, Sweden) was one of the pioneers on the subject, showing through epidemiology that the partial loss of the Y chromosome, which increases with age and smoking – it is detectable in 40% of men aged 70 and 57% of those aged 93 – was associated with an increased risk of cancer, cardiovascular disease and Alzheimer’s, and a reduction in life expectancy. “But the question remained whether it was actually causative, or just a sign of aging, a question that epidemiology could not answer”notes Jean-Charles Lambert.

A cascade of reactions

This is the reason why Lars Forsberg and an international team of researchers have developed a mouse model in which the hematopoietic cells, at the origin of the different lines of blood cells (red and white blood cells in particular), lacked a chromosome. Y. These rodents had a shortened life expectancy, and signs of cardiomyopathy and heart failure in older ones. Fibrosis was observed not only in the heart muscle, but also in the lungs and kidneys.

The researchers then returned to epidemiology, drawing data from the UK Biobank on a large sample of men, whose percentage of mLOY among blood cells was known. It shows that those with a mLOY at the start of the observation period for more than 40% of leukocytes – the famous white blood cells of the immune system – had a 31% increased risk of dying from a disease of the circulatory system. ten years later, and a 41% increased risk for any cause of death.

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