By Mark Waghorn via SWNS
Men have a shorter lifespan than women because the loss of the male sex chromosome as they age damages their heart, according to new research.
The lack of a Y chromosome can cause heart scarring and lead to deadly heart failure.
The finding sheds light on why women live several years more, on average.
Lead author Professor Kenneth Walsh, of the University of Virginia, said: "Particularly past age 60, men die more rapidly than women. It is as if they biologically age more quickly.
"There are more than 160 million males in the United States alone. The years of life lost due to the survival disadvantage of maleness is staggering.
"This new research provides clues as to why men have shorter lifespans than women."
A child's gender is determined by chromosomes - known as X and Y. They carry our DNA. Males have XY while females have XX.
Fathers contribute the X or Y, and mothers an X. Inherit an X and Y and you are a boy. Get a pair of Xs and you are a girl.
It is surprisingly common for men to lose the Y chromosome from blood cells as they age. The phenomenon affects an estimated four in ten 70-year-olds.
They may benefit from an existing drug that targets dangerous tissue scarring, said Walsh.
It could counteract the harmful effects of chromosome loss – not just in the heart but in other parts of the body as well.
In the US, women live an average of five years longer. The discovery may explain nearly four of those years, said Walsh.
A similar phenomenon occurs in the UK with an expected lifespan ranging from 76 for men in Scotland to 83 for women in England.
Male smokers are most prone to losing the Y chromosome. It occurs predominantly in cells that undergo rapid turnover, such as blood cells.
Loss of the Y chromosome does not occur in reproductive cells, so it is not inherited by the children of affected men.
Previous research has shown men who suffer Y chromosome loss are more likely to die at a younger age and suffer age-associated diseases such as Alzheimer's.
But the study in the journal Science is the first hard evidence it directly impacts health.
Walsh and colleagues used a gene editing technique called CRISPR - likened to a pair of molecular scissors - to develop a mouse model of Y chromosome loss in the blood.
They found it accelerated age-related diseases, made the mice more prone to heart scarring and led to earlier death.
This wasn't the result of just inflammation. Instead, the animals suffered a complex series of responses in the immune system.
It leads to scarring, or fibrosis, throughout the body. Walsh described it as a 'tug-of-war'.
The scientists also looked at the effects in men by analyzing data from the UK Biobank, an ongoing project that tracks the health of half a million Britons.
They found that Y chromosome loss was associated with cardiovascular disease and heart failure.
The risk of premature death rose in tandem with increased loss of the chromosome.
Targeting the effects could help men live longer, healthier lives, said Walsh.
One potential drug, pirfenidone, has already been approved by the US Food and Drug Administration for the treatment of lung scarring.
It is also being tested for heart failure and chronic kidney disease, two conditions for which tissue scarring is a hallmark.
Based on his research, Walsh believes men lacking the Y chromosome could respond particularly well to the drug.
Other classes of antifibrotic drugs are also being developed.
At the moment, doctors have no easy way to screen patients.
Co-author Professor Lars Forsberg, of Uppsala University, Sweden, has developed an inexpensive Covid-style PCR (polymerase chain reaction) test that can detect Y chromosome loss. It is not yet ready for clinical trials.
Added Walsh: "If interest in this continues and it is shown to have utility in terms of being prognostic for men's disease and can lead to personalized therapy, maybe this becomes a routine diagnostic test.
"The DNA of all our cells inevitably accumulate mutations as we age. This includes the loss of the entire Y chromosome within a subset of cells in men.
"Understanding the body is a mosaic of acquired mutations provides clues about age-related diseases and the aging process itself.
"Studies that examine Y chromosome loss and other acquired mutations have great promise for the development of personalized medicines that are tailored to these specific mutations."
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