Age-related loss of the Y chromosome — the part of human DNA unique to men — increases men’s risk of potentially life-threatening heart problems as they age, new research suggests.
The discovery, described in the journal Science, paves the way for a simple test to identify men whose Y chromosome count puts them at higher risk for conditions such as heart failure, in which a diseased heart struggles to pump blood around the body.
Humans have two sex chromosomes, X and Y. Males usually have one of each, while females have two X chromosomes.
Scientists have known for decades that some men begin to lose Y chromosomes from their cells as they age.
Age-related loss of the Y chromosome — the part of human DNA unique to men — increases men’s risk of potentially life-threatening heart problems as they age, new research suggests
For example, a previous study of thousands of men in the UK found that the chromosome was absent in about a fifth of 40- to 70-year-olds. This phenomenon, known as Y loss, has been linked to a range of health problems, including cancer, cardiovascular disease and Alzheimer’s disease, as well as a shorter lifespan.
However, scientists couldn’t determine whether the loss of the Y chromosome directly caused disease or whether it, like wrinkles or graying hair, was simply a sign of aging.
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Now, for the first time, scientists have shown that loss of Y chromosome can harm the heart. (Women also experience a loss of their sex chromosomes, but this has not been associated with shorter lifespans and disease.)
The scientists, from the University of Virginia in the US and Uppsala University in Sweden, first proved the link in mice.
They showed that mice without the Y chromosome of their white blood cells (loss of Y chromosome is easiest to measure in white blood cells) died earlier than mice that still had their Y chromosomes.
The mice with few Y chromosomes also developed more fibrosis — or thickening — of their heart muscles. This thickening stiffens the heart and makes it more difficult for it to pump blood.
The researchers then moved on to people, looking at medical and genetic information on more than 223,000 men who gave blood samples to the UK Biobank, a large health database.
They found that men who lost the Y chromosomes of more than 40 percent of their white blood cells were 31 percent more likely to die from heart disease, including heart failure, over the following 12 years than those who didn’t. Y loss.
The researchers concluded that these results together indicate that Y loss contributes to heart muscle fibrosis, cardiac dysfunction and mortality in men.
They speculate that the loss of the Y chromosome affects how some cells in the heart work, causing fibrosis and heart disease.
Professor Kenneth Walsh, who led the study, told Good Health: ‘As we age, one of the things that happens is that we develop fibrosis in various tissues and organs, including the heart, kidneys and lungs. And that process is accelerated by loss of the Y chromosome.’
However, the rate of loss of Y chromosome varies. “Some men lose it very quickly — they’re super losers — but others don’t, and we don’t understand why that is yet,” says Professor Walsh.
In the future, testing for Y chromosome loss could lead to the identification of the ‘super losers’.
“If you’re one of those men who lose a lot of their Y chromosomes, that could be an indication to see a specialist who can do a cardiac MRI scan to measure the degree of fibrosis,” says Professor Walsh.
While there is currently no treatment for heart fibrosis, scientists are working on new drugs to reverse the damage.
Professor John Perry, a geneticist at the University of Cambridge who has studied Y loss, said the findings were interesting but urged men not to worry, saying: ‘It is a very modest risk factor for heart disease compared with other factors that are more significant, such as blood pressure, weight, and “bad” LDL cholesterol.
“These other factors are modifiable, when you really can’t do anything about Y-loss,” he says.
“The only light evidence for this is that if you smoke and you stop smoking, the Y loss can go down a little bit.”
“The ultimate hope here is that we can tackle Y loss, neutralize the effects of Y loss and have a healthy heart as a result,” adds Dr Mikhail Spivakov, a geneticist at Imperial College London.