Why men live less than women: the genetic defect that explains it is discovered

Loss of the male sex chromosome (Y) in old age causes heart muscle to scar and can lead to fatal heart failure, but it could also be the reason why men live, on average, a few years less than women.

These are the main conclusions of a study conducted by Kenneth Walsh, a researcher at the University of Virginia School of Medicine (USA), which suggests that men who lose the Y chromosome — it is estimated that they represent 40% of people aged 70 – could benefit from a drug that heals damaged tissue.

According to the survey, published this Thursday in the magazine Sciencethis medicine could counteract the harmful effects of chromosome loss, which can manifest not only in the heart, but also in other parts of the body.

In the United States, women live an average of five years longer than men. The finding from this study “could explain nearly four of those five years of difference,” according to Walsh.

“Especially after 60, men die faster than women. It’s like aging biologically faster. This research gives clues as to why men have shorter lives than women,” adds the researcher.

While women have two X chromosomes, men have an X and a Y, but with age many begin to lose the Y chromosome in part of their cells, which is especially safe in smokers.

It had been observed that men who suffer from the loss of the Y chromosome in their white blood cells are more likely to die younger and to suffer from age-related diseases like Alzheimer’s disease, but so far the cause had not been identified.

Walsh’s research is the first to show that this loss has deleterious effects on men’s health.

The investigation

To do the research, Walsh and his team used the CRISPR gene editing technique and developed a special mouse model to study the effects of Y chromosome loss in the blood of mice.

They found that this loss accelerated age-related diseases, made the mice more prone to heart scarring, and led to earlier death.

But for the scientists, it wasn’t the result of simple inflammation: rather, the mice underwent a complex series of immune system responses that led to a process called fibrosis throughout the body.

The authors believe that this push and pull of the immune system can hasten the development of the disease.

Cardiovascular illnesses

The team also looked at the effects of Y chromosome loss in men using data collected from the UK Biobank. They found that Y chromosome loss was associated with cardiovascular disease and heart failure, and that as chromosome loss increased, so did the risk of death.

These findings suggest that countering the effects of Y-chromosome loss could help men live longer, healthier lives.

For Walsh, a possible treatment option could be a drug, pirfenidone, which has already been approved by the Federal Food and Drug Administration (FDA) to treat idiopathic pulmonary fibrosis, a form of lung scarring.

The drug is also being tested for the treatment of heart failure and chronic kidney disease, two conditions that cause tissue scarring.

Walsh thinks men with Y-chromosome loss may respond particularly well to this drug and other classes of anti-fibrotic drugs in development, though more research is needed to find out.

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