Monday, 5 Dec 2022

Loss of male sex chromosome leads to earlier death for men: Causes potentially deadly heart scarring; existing drug may offer treatment option

The loss of the male sex chromosome as many men age causes the heart muscle to scar and can lead to deadly heart failure, new research from the University of Virginia School of Medicine shows. The finding may help explain why men die, on average, several years younger than women.

UVA researcher Kenneth Walsh, PhD, says the new discovery suggests 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, he suspects, may help counteract the harmful effects of the chromosome loss — effects that may manifest not just in the heart but in other parts of the body as well.

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.

“Particularly past age 60, men die more rapidly than women. It’s as if they biologically age more quickly,” said Walsh, the director of UVA’s Hematovascular Biology Center. “There are more than 160 million males in the United States alone. The years of life lost due to the survival disadvantage of maleness is staggering. This new research provides clues as to why men have shorter lifespans than women.”

Chromosome Loss and Heart Health

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. The loss occurs predominantly in cells that undergo rapid turnover, such as blood cells. (Loss of the Y chromosome does not occur in male reproductive cells, so it is not inherited by the children of men who exhibit Y chromosome loss.) 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. Walsh’s new research, however, is believed to be the first hard evidence that the chromosome loss directly causes harmful effects on men’s health.

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