Gene mutation makes men live shorter than women, study finds

Gene mutation makes men live shorter than women, study finds

In addition to men smoking, drinking and exposing themselves to reckless acts more often than women, a study shows that men age faster than women, which may help explain why they live shorter. The article, published in the journal Science, revealed that a mutation of the Y chromosome in blood cells increases the risk of heart problems and immune system failure.

Until then, it was not possible to explain whether the gradual disappearance of the chromosome in the blood played a role in causing diseases associated with aging. The study was released in July this year.

The publication is the continuation of a series of investigations started in 2014 by the team of researcher Lars Forsberg, from the University of Uppsala, Sweden. The initial research looked at life expectancy in older men with blood cells that had lost the Y chromosome with age, in a mutation known as mLOY. The effect recorded was “huge,” according to the study group.

According to research, men with fewer Y chromosomes had a higher risk of developing cancer, and lived an average of five and a half years shorter than those who had not lost this part of their genome. In another study, Forsberg and his team found a link between the mLOY mutation and Alzheimer’s: men with this trait were three times more likely to have the degenerative disease.

Scientists have identified that 20% of men over 60 years old have the mutation on the Y chromosome. From the age of 70, the rate rises even more, affecting 40% of males. “It is by far the most common mutation in humans,” explains Forsberg.

Biochemist and co-author of the article Kenneth Walsh, from the University of Virginia, in the United States, explained to El País that the genetic factor can explain more than 75% of the difference in life expectancy between men and women over 60 years old. The researcher’s calculation was made from the study that indicated a four-year reduction in life in men with a high mLOY load.

The study

The group’s most recent research involved altering the blood stem cells of mice, which were bred to lack the Y chromosome. The work showed that these rodents developed fibrosis, one of the most common cardiovascular diseases in humans, and died earlier than than normal mice. The damage was reversed when the researchers gave the mice pirfenidone, a drug approved in humans to treat the disease.

After animal testing, the authors analyzed the life expectancy of nearly 15,700 patients with cardiovascular disease from data in the UK public biobank. In humans, the conclusions were that the loss of the Y chromosome in the blood is associated with a 30% increase in the risk of death from cardiovascular disease.

The survey also revealed how the fibrosis process takes place and identified the molecular keys responsible for the damage associated with the mLOY mutation. When there is loss of the Y chromosome, an abnormal behavior of macrophages, a type of defense cell in the blood, begins. The action forms scar tissue in the heart tissue, known as fibrosis, increasing the risk of heart failure.

How does the loss of the Y chromosome happen?

There are three risk factors responsible for increased loss of the Y chromosome: the first two are aging and other inherited genetic mutations, both of which are unavoidable. The third is smoking: “Smoking causes you to lose the Y chromosome in the blood at an accelerated rate; and if you stop smoking, the healthy cells are in the majority again”, explains Walsh.

The two scientists believe that the study opens up a “huge” scope for the field of genetic research. They say it is necessary to study whether men with the mLOY mutation also have heart fibrosis, and whether it is the cause of heart attacks and other diseases. The authors also want to better understand why losing the Y chromosome is harmful to health.

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