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July 18, 2022

Many men lose their Y chromosomes as they age. Is that dangerous?

Daily Briefing

    While experts have known for years that many men lose their Y chromosomes in some blood cells as they age, they were unsure whether it was just an innocuous sign of aging, like graying hair. But a new study published Thursday in Science found that mosaic loss of the Y chromosome in blood cells triggered scar tissue build up in the heart of male mice, resulting in heart failure and a shorter life span, Gina Kolata reports for the New York Times.

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    Study details and key findings

    For the study, researchers analyzed a group of male mice that were genetically engineered to lose their Y chromosomes.

    According to Kenneth Walsh, director of the Hematovascular Biology Center at the University of Virginia School of Medicine, the mice initially seemed fine after the Y chromosome left their blood cells. However, Walsh noted that "they aged poorly."

    Ultimately, the mice developed scar tissue in their hearts, kidneys, and lungs. They also experienced non-ischemic heart failure—a poorly understood condition that is not the result of a heart attack. Their life spans shortened, and they suffered a marked decline in their mental abilities.

    Since the research demonstrated a causal relationship between Y chromosome loss and harmful effects of aging in mice, it suggests that loss of the Y chromosome could have a similar effect in humans.

    Walsh, along with Lars Forsberg, a researcher at Uppsala University, analyzed data from 223,173 men from the UK Biobank.

    In their analysis, they determined that men who experienced mosaic loss of Y had a 41% higher risk of dying from any cause during a seven-year follow-up period and a 31% higher risk of dying from a cardiovascular disease. Notably, risk increased as the number of cells that lost the Y chromosome increased.

    Commentary

    So-called mosaic loss of Y occurs, occurring to the New York Times, when the Y chromosome is "kicked out of some cells and then disintegrates" during cell division. Research has found that, among human males, more than 40% experience some loss of Y chromosomes in their blood cells by age 70—and by age 93, that share increases to more than 57%.

    And researchers have increasingly found that chronic disease risk is associated with loss of the Y chromosome. According to the study's authors, the phenomenon could even help explain why women typically have longer lifespans than men.

    "The authors really nailed it here," said Ross Levine, deputy physician in chief for translational research at Memorial Sloan Kettering Cancer Center. "It's super important work."

    Researchers do not know of ways that men can protect themselves from losing their Y chromosomes, nor how they can mitigate the consequences.

    Notably, Walsh's research group found they could help protect the animals' hearts by blocking TGF-beta—a vital molecule involved in scar-tissue production.

    Stephen Chanock, director of the division of cancer epidemiology and genetics at the National Cancer Institute, said the mouse study was "really cool." However, he noted that there is currently no evidence that drugs that block TGF-beta would be effective in men who lost their Y chromosome.

    For now, Chanock argued that there is little point in testing men for loss of Y, adding, "the over-interpretation of these data for monetary purposes worries me deeply." (Kolata, New York Times, 7/15)

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