Scientists have unearthed findings that help to explain why men typically die several years younger than women in a first-of-its-kind study.
Their shorter lifespan has now been linked to the loss of the male sex chromosome (made up of DNA) that happens as many men age, which can cause the heart muscle to scar, and potentially lead to heart failure, research from University of Virginia School of Medicine finds.
Estimates show 40% of 70-year-olds suffer this 'Y' chromosome loss, with the new discovery suggesting these men could benefit from an existing drug that targets dangerous tissue scarring.
"Particularly past age 60, men die more rapidly than women. It's as if they biologically age more quickly," says Kenneth Walsh, PhD, director of University of UVA's Hematovascular Biology Center.
"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."
On average, as women live five years longer than men in the US, for example, Walsh estimates the new finding may explain as many as nearly four years of the difference.
While women have two X chromosomes, men have an X and a Y. Many men begin to lose their Y chromosome in a fraction of their cells as they age, which appears to be particularly true for smokers.
This loss occurs mainly in cells that rapidly change, like blood cells, while it does not occur in male reproductive cells.
The modal age (largest number) at death in the UK in 2018-2020 was 86.7 years for males and 89.3 years for females, in comparison with 86.5 years and 89.0 years respectively in 2015-2017, according to the Office for National Statistics (ONS).
The median age at death was 82.3 years for males and 85.8 years for females, in comparison with 82.4 years and 85.8 years in 2015-2017.
While scientists previously found that men who suffer Y chromosome loss are more likely to die at a younger age and suffer age-associated diseases like Alzheimer's disease, the new research is believed to be the first hard evidence that it directly causes harmful effects on men's health.
“This is the best evidence to date” that losing the Y chromosome is detrimental to health, says John Perry, a human geneticist at the University of Cambridge, Science journal reports. He led one of the biggest studies of the male sex chromosome loss, but wasn't involved in the new research.
Walsh suspects that the drug called pirfenidone may help counteract the harmful effects of the chromosome loss, which may not just have implications for the heart, but other parts of the body too.
Walsh, of UVA's Division of Cardiovascular Medicine and the Robert M. Berne Cardiovascular Research Center and his team used cutting-edge gene-editing technology to develop a special mouse model to better understand the effects of Y chromosome loss in the blood.
They found the loss accelerated age-related diseases and made the mice more prone to heart scarring and led to earlier death, with the results published in the Science journal.
The scientists also assessed the effects of Y chromosome loss in men, conducting three analyses of data from the UK Biobank, a huge biomedical database. They found the Y chromosome loss was associated with cardiovascular disease and heart failure.
As chromosome loss increased, so did the risk of death.
But good news is that the findings suggest that targeting the effects of Y chromosome loss could help men live longer, healthier lives.
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