Scientists from the University of Virginia found that the loss of the male sex chromosome as many men age causes the heart muscle to scar and can lead to deadly heart failure.
The finding may help explain why men die, on average, several years younger than women.
The team also found that men who suffer Y chromosome loss—estimated to include 40% of 70-year-olds—may particularly benefit from an existing drug that targets dangerous tissue scarring.
The drug may help counteract the harmful effects of chromosome loss—effects that may manifest not just in the heart but in other parts of the body as well.
The study was conducted by Kenneth Walsh et al.
On average, women live five years longer than men in the United States. The new finding, Walsh estimates, may explain nearly four of the five-year difference.
While women have two X chromosomes, men have an X and a Y. But many men begin to lose their Y chromosome in a fraction of their cells as they age. This appears to be particularly true for smokers.
Scientists previously observed that men who suffer Y chromosome loss are more likely to die at a younger age and suffer age-associated maladies such as Alzheimer’s disease.
The new research is believed to be the first hard evidence that chromosome loss directly causes harmful effects on men’s health.
The team used cutting-edge CRISPR gene-editing technology to develop a special mouse model to better understand the effects of Y chromosome loss in the blood.
They found that the loss accelerated age-related diseases, made the mice more prone to heart scarring, and led to an earlier death. This wasn’t the result of just inflammation, the scientists determined.
Instead, the mice suffered a complex series of responses in the immune system, leading to a process referred to as fibrosis throughout the body.
This tug-of-war within the immune system, the researchers believe, may accelerate disease development.
The scientists also found that Y chromosome loss was associated with heart disease and heart failure men. As chromosome loss increased, the scientists found, so did the risk of death.
The findings suggest that targeting the effects of Y chromosome loss could help men live longer, healthier lives.
The team notes that one potential treatment option might be a drug, pirfenidone, that has already been approved by the federal Food and Drug Administration for the treatment of idiopathic pulmonary fibrosis, a form of lung scarring.
The drug is also being tested for the treatment of heart failure and chronic kidney disease, two conditions for which tissue scarring is a hallmark.
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