Loss of Y Chromosome in Mice May Lead to Heart Failure

A new study suggests the same loss in humans may lead to increased mortality

Most individuals born male have an X and a Y chromosome, while those born female have two X chromosomes.  Steven Puetzer via Getty Images

Sometimes individuals born with an X and a Y chromosome—most men and trans women—lose a Y chromosome in a fraction of their cells as they age. This happens to at least 40 percent of those born male by age 70 and at least 57 percent of those borm male by age 93, writes the New York Times’ Gina Kolata. 

Y chromosome loss is linked to increased mortality, but until recently, it was unclear whether the loss was just a benign sign of aging—like gray hair and wrinkles—or whether it actually contributed to disease. 

In a study published in Science, researchers used the gene-editing tool CRISPR on mice to destroy the Y chromosome in some of their white blood cells. For the first time, they discovered that this loss led to direct damage on internal organs and shorter lifespans, per a statement

“We found that while loss of the Y chromosome did not have immediate effects on the young mice, they ended up aging poorly, dying at an earlier age than mice that still had Y chromosomes,” writes co-author Kenneth Walsh, a professor of internal medicine at the University of Virginia for The Conversation. “They also had more buildup of scar tissue in the heart, a condition called fibrosis, as well as a stronger decline in heart function after induced heart failure.” 

The researchers examined health data from humans with a Y chromosome to corroborate this causal effect. Using the UK Biobank—a database with genetic and medical information from 500,000 individuals between 40 and 69 years—the team found that individuals who had lost their Y chromosomes in over 40 percent of their white blood cells were at a 31 percent increased risk of dying from cardiovascular disease, per the statement. They also had a 41 percent increased risk of dying from any cause. 

“We believe that a better understanding of how the Y chromosome may contribute to age-related diseases, and potentially the process of aging itself, could lead to ways to screen and prevent excessive tissue scarring that can lead to cardiovascular disease,” Walsh writes for The Conversation

The study focused on the heart, but the research team also found scarring on kidneys and lungs and accelerated cognitive impairment in mice with Y chromosome loss. 

“The authors really nailed it here,” Ross Levine, the deputy physician in chief for translational research at Memorial Sloan Kettering Cancer Center, tells the Times. “It’s super important work.”

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