Scientists have discovered a possible reason why men die younger than women, finding that those who lose Y chromosomes from their blood cells as they age may be more likely to have scarring of heart tissue and heart failure.
The research is the latest looking at the phenomenon of “Y chromosome loss” – where the Y chromosome disappears from part of a man’s blood cells.
Researchers don’t know why it occurs, but it’s linked to aging: it can be detected in 40% of men by age 70, and more than half of those who live into their 90s.
At one point, researchers thought the loss of the Y chromosome – a small, tortuous chromosome – was just part of normal aging.
But in recent years, studies have linked Y loss to an increased risk of diseases such as Alzheimer’s, heart disease, and certain types of cancer, as well as shorter life.
However, those studies couldn’t show whether chromosome loss directly contributes to disease, or just a sign that other body processes are going backwards.
“The question is…is losing Y just a sign of aging like graying hair?”
Study co-author Kenneth Walsh, who directs the Center for Vascular Biology at the University of Virginia School of Medicine, said the study found that the loss of Y in blood cells made heart tissue vulnerable to scarring and led to early death.
“It’s evidence that chromosome loss is a direct factor, not just a bystander.”
Most people define the Y chromosome as a sex chromosome: women have two X chromosomes, while men have an X and a Y.
Researchers used to think that the Y chromosome determined male sexual characteristics, but studies in recent years have found that the Y chromosome contains more genes than previously thought – and their functions are completely unknown.
Parallel to this work, research has linked Y loss to various disease risks. To find out why, Walsh and his team conducted studies in both humans and lab mice and used a large research database containing medical and genetic information on nearly 500,000 British adults.
They found that men who took part in that study with a significant loss of Y – in more than 40% of their blood cells – fared worse over the following years.
41% of them were more likely to die from any cause over the next seven years, versus men who did not lose Y.
Specifically, they were two to three times more likely to die from heart failure or heart disease associated with prolonged high blood pressure.
To directly test the effects of Y loss, Walsh’s team used “gene editing” technology to create lab mice that lacked the chromosome in many of their blood cells.
They found that in elderly male mice, loss of Y accelerated age-related changes in heart structure and function, and made the animals more susceptible to scarring in the heart, as well as the lungs and kidneys. In one experiment, the loss of the chromosome exacerbated existing heart failure.
Walsh said the loss of the Y chromosome appears to alter the function of immune cells that function in the heart, leading to tissue scarring.