Men who lose the Y chromosome in many immune cells face higher risks of narrow blood vessels. Narrowed vessels are a key driver of heart disease. This conclusion comes from a study analyzing more than 30,000 people.
“Loss of Y is killing a lot of men,” said Kenneth Walsh at the University of Virginia, who wasn’t involved in the study. “Men live six years shorter than females, and an enormous amount of that mortality is due to their sex chromosome instability.”
How Y chromosome loss occurs
As men grow older, some of their cells start losing the Y chromosome. This usually happens in white blood cells, which protect the body from infections.
When new blood cells are made, small mistakes can occur, and more cells lose the Y chromosome over time. By age 70, about 4 out of 10 men have this loss.
In 2014, researcher Lars Forsberg found that men with Y loss lived about five years less than those without it. Later, Kenneth Walsh linked this loss to a higher risk of heart disease.
Y chromosome loss and heart disease
The Swedish CArdioPulmonary Bioimage Study (SCAPIS) offers one of the largest datasets for exploring cardiovascular risk.
The researchers studied over 30,000 participants aged 50 to 64, including detailed imaging of their coronary and carotid arteries.
Men with substantial Y loss in blood cells showed stronger links to coronary atherosclerosis than men without it.
This included more severe narrowing of arteries, greater numbers of affected vessel segments, and higher levels of calcified plaque.
Y chromosome loss and heart arteries
The researchers found that when men lose the Y chromosome in their blood cells, it links strongly to heart problems, especially in the coronary arteries, which supply blood to the heart.
But this same loss does not seem to affect the carotid arteries in the neck in the same way. The reason may be that these two types of arteries develop disease for different reasons.
Coronary artery disease is mainly caused by fat and cholesterol building up inside the blood vessels. This buildup, combined with inflammation, leads to plaque that blocks blood flow to the heart.
Losing the Y chromosome seems to make these processes worse, increasing the chances of clogged or narrowed heart arteries.
Carotid artery disease, on the other hand, is more often linked to high blood pressure and the stress of blood flow against artery walls. Because of this, the Y chromosome loss may not play as large a role in the carotids.
This difference shows that Y chromosome loss may affect some parts of the body more than others. It also helps explain why men, who are more likely to lose the Y chromosome, often have higher risks of heart disease compared with women.
How Y loss harms cells
Researchers have observed that immune cells lacking Y often show disrupted gene regulation and impaired function.
In animal models, Y loss triggered fibrosis in heart and lung tissue, driven by heightened TGF-β signaling. Blocking this pathway reversed damage, suggesting a direct mechanistic role.
In humans, men with Y loss display fibrotic disease patterns and an increased risk of both pulmonary and cardiac complications.
Together, these findings imply that Y loss contributes to plaque formation, fibrous cap buildup, and calcification – features linked with coronary disease severity.
Y loss raises heart risk
Losing the Y chromosome is more than just a sign of aging. It directly raises men’s risk of heart disease, leading to earlier and more severe artery problems.
This risk stays even when factors like smoking, weight, diabetes, or cholesterol are considered.
Kenneth Walsh notes that more proof is needed, but evidence from scans, genetics, and lab studies strongly suggests Y loss makes men more vulnerable to heart disease.
Testing Y loss for treatment
Researchers envision a simple blood test to identify men with significant Y loss. This could help guide preventative strategies, such as closer monitoring, targeted therapies, or lifestyle interventions.
“It might identify patients who will particularly benefit from specific treatments,” said Thimoteus Speer.
The emerging view is that Y chromosome loss reshapes immune cell behavior, driving both fibrotic and atherosclerotic pathways. This dual effect could explain men’s shorter lifespans and higher rates of heart disease.
As understanding deepens, detecting and managing Y loss may become central in men’s cardiovascular care.
Scientists believe this finding could change how doctors treat men’s heart health. If doctors test for Y loss early, they could spot which men are at higher risk.
With that knowledge, doctors could watch these patients more closely, suggest healthier habits, or create treatments to lower the danger.
The study is published in medRxiv.
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