Might the lack of the Y chromosome contribute to the early loss of life of males?

This could partly explain why men, on average, die earlier than women. The loss of the Y chromosome occurs in some men as they age. In some, this loss can affect up to 80% of the cells!

Researchers at the University of Virginia have shown that this phenomenon can have major consequences for men’s health, mainly because it causes heart failure. They published their results in the journal Science (Click here to read the study).

The Y chromosome: so small and so understudied

This loss of the Y chromosome mainly occurs in cells that renew rapidly, such as blood cells. This particular male chromosome is relatively small in size and contains few genes: the equivalent of less than 10% of the number of genes on the X chromosome! Difficult to study, there is little information about its biological role, other than sex determination.

Recent publications have already indicated that the loss of the Y chromosome may be associated with a shorter lifespan and the risk of developing Alzheimer’s disease. In this study, researchers found other consequences of this disappearance on men’s health.

The consequences of this loss: an increase in the number of fibrosis…

To study the impact of the loss of the Y chromosome, the researchers measured the effects of its deletion in mice.

They used the CRISPR-Cas9 gene editing tool to delete the Y chromosome from the mice’s bone marrow cells. The researchers then inserted the modified cells into young male mice whose bone marrow had previously been removed.

This eliminated the Y chromosome in 49-81% of white blood cells. This is about the same percentage as in many men with Y chromosome loss.

They followed these mice for 600 days. At the end of this period, only 40% of these mice survived after transplants of cells without the Y chromosome. Against about 60% for the control mice.

This is not everything. This loss also had impacts on the heart. After 15 months, the force of contraction of the heart decreased on average by almost 20%! The mice had a buildup of fibrosis, that is, a buildup of hard connective tissue due to excessive collagen synthesis. This fibrosis is triggered in part by macrophages lacking a Y chromosome. These cells lead to the proliferation and activation of fibroblasts – which secrete collagen. This will promote heart failure, a major cause of mortality and morbidity in the elderly.

Read too: Do optimists really live longer? What does science say…

…and an increase in the number of deaths.

The researchers cross-referenced this experiment with other data. Those of the survival rate of men who lack the Y chromosome in most of their cells. Extracted data from UK Biobank and performed 3 types of analyses. The goal ? To determine whether loss of the Y chromosome in white blood cells is associated with risk of death from cardiovascular disease.

The results are final. The risk of dying during follow-up for a circulatory system disease was increased by 31% in men with more than 40% of Y-chromosome-free white blood cells (for a median follow-up of 11.5 years).

This included deaths from high blood pressure, heart failure, or even an aneurysm.

In addition to heart disease, this loss of the Y chromosome impacts men’s overall health. The researchers analyzed other data from the UK Biobank, with shorter follow-up time (median follow-up of 7 years). They found that the risk of dying from any cause increased by 41% in men whose white blood cells were more than 40% missing a Y chromosome.

This new research provides clues as to why men have a shorter life expectancy than women. — Kenneth Walsh, study co-author and professor at the University of Virginia

Detect the loss of the Y chromosome

At the moment, there is no easy way to establish which men suffer from chromosome loss. Y. Lar A. Forsberg of Uppsala University in Sweden has developed an inexpensive test. For this, he uses the PCR method to detect the loss of the Y chromosome. However, this test has not been extended beyond his laboratory, but one day it may be the case.

If interest in this test continues and proves useful in terms of prognosis of disease in humans and could lead to personalized therapy, it could become a routine diagnostic test. . – Home A. Forsberg

Read too: Alopecia: Discovery of a link between the immune system and hair growth. Researchers have highlighted the cellular mechanism induced by a common treatment for alopecia, which makes it possible to generate new hair follicles.

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