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Why Men Die, On Average, Several Years Younger Than Women – New Study Finds

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In the US, women typically live five more years than men do. The study authors think that the new finding could explain almost four of the five-year difference.

According to new research from the University of Virginia School of Medicine, the loss of the male sex chromosome as men age causes the heart muscle to scar and can result in fatal heart failure.

The discovery could help explain why men die several years younger than women.

Kenneth Walsh, PhD, a researcher at the University of Virginia, says the new study shows that males with Y chromosome loss – which is believed to affect 40 percent of 70-year-olds – may benefit most from an existing medicine that targets dangerous tissue scarring.

He believes that the medication could help mitigate the negative effects of chromosomal loss, which could emerge not only in the heart but in other areas of the body as well.

In the US, women typically live five more years than men do. Walsh speculates that the new finding may account for four of the five-year discrepancy.

“Particularly past age 60,” according to the author, “men die more rapidly than women. It’s 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.”

Loss of Chromosomes and Heart Health

Men have an X and a Y chromosome, whereas women have two X chromosomes. But as men age, a small percentage of their cells start to lose the Y chromosome.

Smokers seem to be an exception to this rule. The loss mostly affects blood cells and other cells that change quickly. Children of men who demonstrate Y chromosome loss do not inherit it because Y chromosome loss does not occur in male reproductive cells.

Men who lose their Y chromosome are more likely to die young and develop age-related diseases like Alzheimer’s disease, according to earlier research.

Walsh’s new research, on the other hand, is thought to be the first solid proof that chromosome loss directly hurts men’s health.

Walsh, of the Division of Cardiovascular Medicine and the Robert M. Berne Cardiovascular Research Center at the University of Virginia, and his team employed cutting-edge CRISPR gene-editing technology to create a unique mouse model to better comprehend the impact of Y chromosome loss in the blood.

The loss increased age-related disorders, rendered the mice more susceptible to heart scarring, and hastened their death. Scientists found that this wasn’t just caused by inflammation.

Instead, the mice experienced a complicated series of immune system reactions that resulted in a condition known as fibrosis across the body.

The researchers hypothesize that this immune system struggle could hasten the onset of illness.

The repercussions of Y chromosome loss in male humans were also studied by the researchers.

They performed three studies on data taken from the UK Biobank, a huge biological database, and discovered that Y chromosome loss was linked to heart failure and cardiovascular illness.

Scientists found that the chance of dying went up as the number of chromosomes was lost.

Potential Therapy

The results show that males may live longer, healthier lives if the impacts of Y chromosome loss are targeted.

Walsh points out that pirfenidone, a medication already approved by the FDSA for the treatment of idiopathic pulmonary fibrosis, a kind of lung scarring, may be a viable therapy option.

Additionally, the medication is being evaluated for the treatment of heart failure and chronic kidney disease, both of which are characterized by tissue scarring.

According to Walsh’s research, men with Y chromosomal loss may respond particularly well to this medication and other types of antifibrotic medications that are now being researched, however more studies are required to confirm this.

At the moment, there is no simple way for doctors to figure out which men have Y chromosome loss.

An affordable polymerase chain reaction (PCR) test, similar to those used for COVID-19 testing, has been created by Walsh’s collaborator Lars A. Forsberg of Uppsala University in Sweden, however, it is mostly used in Walsh and Forsberg’s labs.

But Walsh sees a change coming: “If interest in this continues and it’s shown to have utility in terms of being prognostic for men’s disease and,” he adds, “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 within men. Understanding that the body is a mosaic of acquired mutations provides clues about age-related diseases and the aging process itself,” according to Walsh.

“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.”

Image Credit: Getty

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