It’s bad enough that some men experience erectile dysfunction as they age. But a new study finds that they are also at risk of an age-related loss of the Y chromosome from their white blood cells. The Y chromosome is a chromosome that only men have; and it might be the reason why men are more likely to die from heart disease, the most common cause of death in humans.
Men have a shorter life expectancy than women. In the U.S., for example, men at birth can expect to live to a little over 76 years, while women typically reach 81, a five-year difference. The shorter life expectancy appears to be possibly related to what geneticists call mosaic Loss of Y, or mLOY. By aged 70, at least 40 percent of men have mLOY from their white blood cells.
Like all chromosomes, the sex chromosomes exist in pairs. Females have two X chromosomes, while males have only one X and a second smaller chromosome, designated Y. The Y chromosome contains genes that trigger male development.
Until recently, this loss of Y was considered unimportant. But researchers have increasingly noted that the loss of the Y chromosome appears to be associated with many human diseases.
In this new study, the researchers first tested mice that were genetically-engineered with a missing Y chromosome to see whether mLOY had any effect on their internal organs. They found that mLOY impacted the organs, particularly the heart which showed more scarring. They also noted that these mLOY mice had shortened life expectancy compared to mice that retained the Y chromosome in their white blood cells.
“Examination of mice with mLOY showed an increased scarring of the heart, known as fibrosis. We see that mLOY causes the fibrosis which leads to a decline in heart function,” Lars Forsberg, Associate Professor at the Department of Immunology, Genetics and Pathology at Uppsala University, and co-leader of the study, said in a statement.
The Swedish and American researchers then corroborated their findings in mice by looking at human epidemiological data. The UK Biobank is a database that contains genomic and health information recorded from more than half a million normally ageing individuals, aged 40–70 years. Data analysis revealed that men with mLOY white blood cells at the start of the study had an approximately 30 percent increased risk of dying from heart failure and other cardiovascular diseases during approximately 11 years of follow-up.
Is there a little blue pill for this threat to male lifespan or is it just another inevitable deterioration associated with aging?
A new FDA-approved drug used to treat lung scarring may also help fight scarring brought on by other diseases, as here, explained the study’s other lead researcher, Kenneth Walsh of the University of Virginia School of Medicine. The drug, pirfenidone, is currently being tested in clinical trials for the treatment of heart failure and chronic kidney disease, two conditions for which tissue scarring is prominent. Based on his research, Walsh believes that men with Y chromosome loss could respond particularly well to this drug, and other classes of antifibrotic drugs.
The researchers have published their findings in Science.