Y chromosome aging may result in an increase in heart risk.
For more than 50 years, it has been known that as men become older, many of their Y chromosomes are lost. But nobody was sure if it made a difference. The absence of Y can just be a clinically insignificant aging marker, similar to grey hair.
Studies now claim that it may matter. a great deal.
Insight is provided by a recent study employing male mice who were genetically altered to lose their Y chromosomes. The study, which was released on Thursday in the journal Science, discovered that when those mice's blood cells lost the Y chromosome, scar tissue accumulated in their hearts, resulting in heart failure and a shorter life span.
The findings support the idea that the same phenomenon can occur in male humans since there was a direct cause-and-effect link between the loss of Y and the symptoms of aging in the mice. In numerous studies over the years, including the most recent one, which incorporated information from a sizable genetic study of the British population, researchers have found a correlation between the loss of the Y chromosome and an increased risk for chronic diseases like heart disease and cancer. According to the authors of the Science study, the loss of Y might even partially explain the variation in life expectancy between men and women.
Dr. Ross Levine, the deputy physician in chief for translational research at Memorial Sloan Kettering Cancer Center, remarked of the authors' work, "The authors absolutely got it here." It's really vital to work,
In 2013, Uppsala University researcher Lars Forsberg saw a former professor on a bus, which served as the catalyst for the current study. The professor told Dr. Forsberg that the Y chromosomes in fruit flies were more significant than was previously thought as their conversation progressed.
The doctor was interested. He had never given the disappearance of Y chromosomes much thought. Nearly the majority of the genes utilized by male cells are genes on the X (female cells use two X), and men have one X and one Y. According to Dr. Forsberg, the Y chromosome is essentially a genetic wasteland.
By the time they reach the age of 70, at least 40% of men lose the Y chromosome from part of their blood cells. And at least 57% had lost part of it by the age of 93.
Occasionally, the chromosome from blood cells is lost during cell division when it is expelled from certain cells and then breaks down. Researchers refer to the outcome as a mosaic loss of Y.
There is no other method to lessen the chance of losing the Y chromosome but to cease smoking. Furthermore, the issue has nothing to do with men's bodies producing less testosterone as they age. Supplementing with testosterone would have no impact and would not undo the effects.
Dr. Forsberg returned to his computer to review data on 1,153 elderly men from the Uppsala Longitudinal Study of Aging Men in order to learn more about the notion his professor had put out.
Dr. Forsberg remarked, "I received the data in a few hours and I was like, "Wow." "I saw that guys who had a significant decrease of Y in a significant fraction of their blood cells only lived 5.5 years as opposed to 11.1 years."
You'll understand my amazement, he added. Naturally, I redid everything.
The discovery held up, and in 2014 he published an article in the journal Nature Genetics stating that a loss of the Y chromosome in blood cells was connected to higher mortality rates and cancer diagnoses.
To test men for the loss of Y, he swiftly formed Cray Innovation and joined as a stakeholder.
Similar analyses were published by other researchers. The loss of the Y chromosome in blood cells was soon linked to heart disease, decreased life spans, and numerous age-related disorders such as solid tumors and blood malignancies. Soon, roughly 20 independent articles demonstrated this relationship.
Dr. Forsberg then received a call from Kenneth Walsh, the Hematovascular Biology Center's director at the University of Virginia School of Medicine. Dr. Walsh's research on a different kind of genetic loss associated with aging—an surge in cancer mutations in blood cells known as CHIP—piqued his curiosity about the loss of Y chromosomes. Dr. Levine opened a CHIP clinic at Sloan Kettering because those with CHIP are more likely to get cancer and heart disease.
The Massachusetts General Hospital's director of preventive cardiology, Dr. Pradeep Natarajan, and other individuals established Ten Sixteen Bio in January with the goal of creating a low-cost test for CHIP and researching therapies to mitigate its effects.
But as Dr. Walsh pointed out, CHIP mutations make up a relatively tiny percentage of the genetic changes that arise with aging.
He said, "What's the remainder of this pie?" He was curious about Y chromosomes and started formulating a strategy to determine whether illnesses and Y chromosome loss in blood cells were causally related. His investigation with mice was the result of it.
The mice were OK at first, but according to Dr. Walsh, "they aged terribly." Their lifespans were reduced, and they acquired scar tissue in their hearts, kidneys, and lungs, as well as a form of non-ischemic heart failure whose source is unclear and which does not come from a heart attack. The animals' mental faculties were also compromised.
During a seven-year follow-up, men with mosaic loss of Y had a 41 percent higher risk of dying from any cause and a 31 percent higher risk of dying from any cardiovascular illness. The danger increased with the number of cells that lost Y chromosomes.
However, the piece also poses the query, What about women? Does one of their two X chromosomes get lost? What about Turner syndrome-affected females? All of their cells are the same as the haphazard collection of blood cells in males who lose their Y chromosome because they are born with only one X chromosome.
Dr. Walsh said that while women can lose one X chromosome with aging, it does not happen as frequently as it does in males. With the exception of a connection to lymphoid leukemia.
The Turner syndrome is unique. Cardiovascular irregularities and non-ischemic heart failure are two health hazards that women who have the syndrome share with males who have lost their Y chromosome. They live shorter lives on average than women with two X do.
It is yet too early to recommend any actions men should take to prevent losing their Y chromosomes or to lessen the effects, except quitting smoking.
Dr. Walsh's team discovered that by inhibiting TGF-beta, a crucial chemical involved in the formation of scar tissue, they could save the hearts of the mice without Y chromosomes.
The National Cancer Institute's division head for cancer epidemiology and genetics, Dr. Stephen Chanock, called the mice research "very cool." However, he pointed out that there was currently no proof that TGF-beta inhibitors would work in men who had lost their Y.
The over-interpretation of these results for financial gain strongly concerns me, Dr. Chanock stated, adding that there is now little use in testing males for loss of Y.
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