The Decrease in Y Chromosomes Due to Age May Lead to Heart Risks in Men

For years, it has been known that Y chromosomes decrease when men age, and the condition was believed to be just related to signs of aging, with no further effect on the human body. As studies progress, it turns out that losing Y chromosomes increases the potential of acquiring severe heart diseases. This discovery was made as part of research published in the online journal Science. The team used male mice as their subject in the experiment.

Based on the reports, the absence of Y chromosomes in the red blood cells of mice can cause scar tissue buildup. The condition was also called mLOY, or mosaic Loss of Y. Apparently, it can lead to heart failure and shortened life span. The effect of losing Y chromosomes has been documented by scientists for many years. Aside from being prone to diseases, the loss of the Y chromosome can be utilized to understand the difference in lifespan between men and women.

Researchers from the University of Virginia and Uppsala University in Sweden determined the age when men get affected by this genetic change. At least 20% of men aged 60 will be affected, whereas 40% of men aged 70 will be affected. The data were all gathered by the lead scientists of the study — Lars Forsberg, Ph.D., and Kenneth Walsh, Ph.D. Their team utilized the CRISPR gene-editing tool to extract Y chromosomes from the mice’s white blood cells. They discovered that mLOY damages the animals’ internal organs. In addition, mice with mLOY died earlier than those without the condition.

“The Y is lost during cell division and is more common in tissues and organs with high cell division rates, such as the blood,” explains Lars Forsberg, Ph.D. “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,” said Forsberg. Most importantly, mLOY is linked to buildup of a particular white blood cell in the heart muscle called cardiac macrophages. Those white blood cells stimulate a signaling pathway to build fibrosis. Part of the experiment was to block the signaling pathway called heart trigger high transforming growth factor β1 (TGF-β1). Once blocked, pathological changes occurred — which could reverse the effects of mLOY.

During the process, the team analyzed the genetic and cardiovascular data of 500,000 people ages 40 to 70. The data was accumulated from the UK Biobank. Some individuals already had mLOY and showed a higher risk of short lifespan due to heart disease. “This observation is in line with the results from the mouse model and suggests that mLOY has a direct physiological effect also in humans,” said Forsberg.

Men with mLOY are prone to a heart disease known as non-ischemic heart failure. Forsberg stated that there are very few treatments available for the disease. Preventive measures must be practiced to not aggravate the medical condition. Routine testing for checking Y chromosomes is recommended.

“mLOY testing of aging males would identify the… men [who] would likely benefit from medical checkups and preventive treatments,” Forsberg said. “Loss of the Y chromosome can be relatively easy to measure. If validated by further research, the loss of Y can be used as a prognostic assay, or it potentially can be used to guide therapies.” An MRI analysis is suggested to distinguish if connective tissues/fibrosis in the heart and other organs is already building up. If signs of buildup were shown, he would be given a prescription for anti-fibrosis medications.

“An FDA-approved antifibrosis medication exists for idiopathic pulmonary fibrosis, and this drug is currently being explored for its utility in conditions that involve cardiac and kidney fibrosis,” Forsberg added. “In addition, there is a lot of interest in developing new fibrosis medications by pharmaceutical companies. It is possible that men with loss of the Y chromosome would have a superior response to these medications.” Further research will be conducted to raise more awareness for mLOY. Therapies for mLOY are limited, making preventive measures essential, such as incorporating a routine for cardiovascular health in your lifestyle.