It could well be traced to a constant loss of the male Y chromosome.

The Y chromosome is one of the sex-determining chromosomes that the man has. While the female is equipped with two X chromosomes, males have an X and a Y chromosome. Researchers have now found in a new study that as many men age, more and more cells lose the Y chromosome. And that may be partly the reason why men tend to have shorter lives than women.

More about sex chromosomes
A sex chromosome is a chromosome that determines sex. In the case of the humans (and most other mammals), two X chromosomes result in the female sex, while an X and a Y chromosome result in the male sex. In birds, butterflies and moths it is just the other way around: there males have the same sex chromosomes and the sex chromosomes of the female are different. A bird with two Z chromosomes is a male. If a bird has a Z chromosome and a W chromosome, then it is a female.

It is known that the life expectancy of women is higher than that of men. “Men are more likely to die after age 60 than women,” said researcher Kenneth Walsh.

Shorter life

Previous research has shown that men in the United States live an average of five years shorter than women. And now Walsh thinks he can explain nearly four of the five-year difference. “It’s like they age faster biologically,” Walsh explains. “The years of life lost due to the survival disadvantage of men are enormous. And our new research provides important clues as to why men have shorter life spans than women.”

Y chromosome

According to Walsh, it can be traced to a constant loss of the male sex chromosome, which mainly disappears from blood cells as men age. When cells divide, the chromosomes are passed on to the new cells in one piece. But sometimes things go wrong and a new cell does not get the Y chromosome. Smoking appears to promote this process and cause the Y chromosome to disappear from blood cells even more frequently. In addition, scientists have previously noted that men who suffer from a loss of the Y chromosome are more likely to die at a younger age from certain age-related diseases, such as Alzheimer’s disease. However, Walsh’s new research is considered the first hard evidence to show that chromosome loss has direct harmful effects on male health.


Walsh and his team rely on experiments with the very latest CRISPR technology. They used this to edit the genes of various mice to better understand the consequences of the loss of the Y chromosome in blood cells. The team found that the disappearance of the male sex chromosome accelerated the emergence of age-related diseases, made the mice more susceptible to heart scarring and led to earlier deaths. This was not just the result of inflammation, the researchers determined. Instead, the mice suffered a complex series of responses in the immune system, leading to a process referred to as fibrosis. “This tug-of-war within the immune system may well accelerate the development of disease,” the researchers write.


In addition, the researchers looked at the effects of the loss of the Y chromosome among men affiliated with the UK Biobank (a huge biomedical database). The team conducted three different analyzes and found that the disappearance of the Y chromosome could be linked to cardiovascular disease and heart failure. And also among these men studied, it appears that the greater the loss of the Y chromosome, the greater the chance of death.


The findings could help men live longer and healthier lives. Walsh argues that men who suffer from a loss of the Y chromosome – an estimated 40 percent of 70-year-olds – can benefit from an existing drug; pirfenidone. This drug targets dangerous tissue scars and is used, among other things, in pulmonary fibrosis. In addition, pirfenidone is being tested for the treatment of heart failure and chronic kidney disease, two conditions characterized by tissue scarring. “This drug could also help counteract the harmful effects of chromosome loss,” Walsh argues.

How do you find out if you have a loss of the Y chromosome? There is currently no easy way to determine that. However, Walsh and his colleagues have developed a test — similar to COVID-19 tests — that can detect a loss of the Y chromosome. However, this test is not yet available outside of Walsh’s lab. However, according to the researcher, this could change in the short term. “If interest in this continues and it indeed proves to be a good predictor of disease in men, the test could potentially be performed more routinely,” concludes Walsh.