Scientists at the University of Virginia have discovered that as men age, they often lose the Y chromosome in some of their blood cells—and this can lead to serious damage in the heart, including scarring and heart failure.
This discovery helps explain why men, on average, live shorter lives than women and suggests new ways to prevent or treat heart problems linked to aging.
In the United States, men live about five years less than women on average. Biologically, men have one X and one Y chromosome, while women have two X chromosomes. Over time, many men begin to lose the Y chromosome in a portion of their cells. By the age of 70, about 40% of men have experienced this chromosome loss. The problem is even more common in smokers.
Scientists have known for some time that losing the Y chromosome might be linked to conditions like Alzheimer’s and early death, but until now, there was no clear proof that it directly causes harm.
This new study, led by Dr. Kenneth Walsh, provides the first solid evidence that the loss of the Y chromosome has real and damaging effects on health—particularly heart health.
To better understand this, the research team used CRISPR gene-editing technology to create a group of mice that had Y chromosome loss in their blood cells, similar to what happens in older men. These mice showed signs of aging more quickly, had more scarring in the heart (a condition called fibrosis), and died earlier than normal mice.
The scientists discovered that the scarring was not just caused by general inflammation. Instead, it involved a complex immune response that led to thickened, stiff tissue not only in the heart but possibly in other organs too. The more Y chromosome loss the mice had, the worse the damage became.
When the researchers looked at human data, they found the same trend. Men who had lost more Y chromosomes were more likely to suffer from heart disease, heart failure, and early death. This means the Y chromosome plays an important role in protecting the heart and other organs as men age.
There’s hope, though. The researchers found that a drug called pirfenidone, already used to treat lung scarring in people with idiopathic pulmonary fibrosis, might also help treat heart problems caused by Y chromosome loss. This drug is currently being tested for other conditions involving organ scarring, like heart failure and kidney disease.
This study also suggests that Y chromosome loss could be one of the biggest reasons why men die younger than women. In fact, it may account for up to four of the five-year difference in life expectancy between the sexes.
The findings highlight how important it is to understand the changes that happen in our genes as we get older. They also raise new questions about how lifestyle factors like smoking might make Y chromosome loss—and the health problems that follow—even worse.
With more research and new treatments, this discovery could lead to better care and longer lives for millions of men.
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