It has always been a mystery why men tend to die, on average, several years younger than women. A recent study by researchers from the University of Virginia School of Medicine suggests that losing male sex chromosomes as men age causes scarring in heart muscles that can lead to life-threatening heart failure.
In the US, women typically live five years longer than men. According to Kenneth Walsh, Ph.D., a UVA researcher, the new findings explain the nearly four of five-year difference between the sexes. Adding that the discovery suggests that men suffering from sex chromosome loss
Negative Impacts of Male Sex Chromosome Loss
Women have two X chromosomes, while men have an X and Y sex chromosome. However, many men begin to lose their Y chromosomes in a fraction of their cells as they get older. This appears to be especially true for smokers. The loss occurs largely in cells that undergo rapid turnover, such as blood cells.
Previously, scientists observed that men suffering the loss of the Y chromosome are more likely to die younger and suffer from age-associated maladies like Alzheimer's.
Walsh collaborating with UVA's Division of Cardiovascular Medicine and the Robert Berne Cardiovascular Research Center, published a study in the journal Science titled "Hematopoietic loss of Y chromosome leads to cardiac fibrosis and heart failure mortality." used CRISPR gene-editing technology to develop specialized mouse model to gain insight on the negative effects of Y chromosome loss in the blood.
The team found that sex chromosome loss accelerated age-related diseases. This made the mice prone to heart scarring and earlier death. The scientists determined that the phenomenon wasn't due to just inflammation. Instead, the mice were observed to suffer from a complex series of immune system responses, leading to a process known as fibrosis throughout the body, reports MedicalXpress.
Experts also looked at the effects of chromosome loss in human men. The team conducted three analyses of data compiled from the UK Biobank. They found that Y chromosome loss was linked with cardiovascular diseases and heart failure. As chromosome loss increases with age, so do the risks of death.
Promising Treatments for Sex Chromosome Loss and its Impacts on Human Health
The recent study's findings suggest that targeting the effects of the Y sex chromosome loss could help human men live longer, healthier lives. Walsh notes that a potential treatment might be a drug, pirfenidone, already approved by the US FDA for treating idiopathic pulmonary fibrosis from lung scarring.
The drug is currently also being tested as a treatment option for heart failure and chronic kidney disease, the two conditions for tissue scarring.
Based on Walsh's research, he believes that men suffering from Y chromosome loss could respond well to the drug and other classes of developed antifibrotic drugs. However, more research is needed to solidify the author's recommendations.
As of now, doctors have no quick way of determining which men are suffering from Y chromosome loss. Walsh's collaborator from Uppsala University, Sweden, Lars A Forsberg, has developed an inexpensive polymerase chain reaction test, similar to testing for COVID-19, that can detect loss of the Y chromosome.
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