Why do men die earlier than women?

As they age, some men lose the Y chromosome in part of their cells. Without it, they are more susceptible to certain diseases. But does that also make them less old?

According to the German Federal Statistical Office, life expectancy for men and women has risen continuously in recent decades, but one difference remains: men still die on average about five years earlier than women. One possible reason for this could be the Y chromosome.

Cells can lose Y chromosome

The so-called X and Y chromosomes belong to the genetic information in our body cells. Women usually have two X chromosomes in their cells, while men only have one – and an additional Y chromosome. This is significantly smaller than the X chromosome and ensures that male sexual characteristics develop in an embryo. However, the Y chromosome can be lost in men during cell division in the course of life.

This has been known in professional circles for a long time. This mutation is not entirely harmless, explains cardiologist Andreas Zeiher, who is researching the subject at Frankfurt University Hospital: „In the last two or three years there have been studies that have shown that if you lose this Y chromosome, you have it more often Cardiovascular diseases, also more frequently Alzheimer’s, diabetes and the classic age-related disease macular degeneration. So when your eyesight slowly fades. And building on that, you naturally thought: How can that be?“

Blood cells affected in particular

The loss of the Y chromosome occurs mainly in hematopoietic cells, which produce billions of blood cells in the bone marrow every day, Zeiher explains. If such a blood stem cell loses its Y chromosome, all its descendants also have no Y chromosome, and often it even produces more new blood cells than others.

About 40 percent of men over 70 are affected by this mutation, Zeiher said, compared with only about five percent of 45-year-olds. But not all blood stem cells lose the Y chromosome; a so-called mosaic of cells with different genetic information is formed.

Connection with heart problems

A research team led by the cardiologist now wants to find out what changes in these cells as a result of the missing Y chromosome. This is because the switching on or off of genes could trigger pathological processes in the body.

To this end, the researchers regularly examine blood samples from male patients of advanced age with heart problems and look for cells with a missing Y chromosome. The results show that blood cells without a Y chromosome are significantly more common in men with heart disease than in healthy men.

Changes in the organs

In animal experiments, a research group in the U.S. has already been able to show the important role that the Y chromosome plays in health. Blood cells without a Y chromosome triggered inflammatory processes in the animals – not only in the heart, but also in the lungs and kidneys.

As a result, the tissue changes into scar tissue, a condition known as fibrosis. Such scarring makes the heart stiffer and less able to pump, Zeiher says. Whether the process can also be transferred to humans has not yet been conclusively clarified. But the cells of the patients at the University Hospital in Frankfurt also produce more substances that trigger inflammation: „From that point of view, we already believe that the findings from the mouse can be transferred to humans.“

No therapy yet

There is still no therapy for the consequences of the missing Y chromosome. It is also not known whether the loss of the Y chromosome could be prevented. But there are certain lifestyle habits that favor the loss. Cardiologist Zeiher therefore recommends that men be physically active, not smoke and avoid stress.

The Frankfurt team hopes to uncover other consequences of the missing Y chromosome in the body and to develop therapies against the medical problems that accompany it.