Many men lose their Y chromosomes as they get older. It was not known if it mattered. The loss of Y could be a sign of old age, like gray hair.
Researchers say that it can matter. Quite a bit.
There is a new study using male mice. The paper, published on Thursday in the journal Science, found that when the Y chromosome was gone from blood cells in the mice, scar tissue built up in the heart, leading to heart failure and a shorter life span.
The study supports the idea that the same thing can happen in humans if Y is lost. Researchers have documented an increase in risk for chronic diseases like heart disease and cancer related to loss of the Y chromosomes in many studies over the years. Some of the difference between the life spans of men and women may be due to the loss of Y.
Other investigators weren't involved in the work.
The authors nailed it, according to Dr. Ross Levine, the deputy physician in chief. It is crucial work.
The inspiration for the new research came when a researcher ran into a professor on a bus The professor said that the Y chromosomes in fruit flies were more important than before.
The doctor was interested. He didn't pay much attention to the Y chromosomes being lost. Males have one X and one Y, and most of the genes used by male cells are genes on the X.
Forty percent of males lose their Y chromosomes by the age of 70. At least 57 percent have lost some of it.
Researchers call it a mosaic loss.
Smoking reduces the risk of losing the Y chromosomes. Men with lower levels of testosterone in their bodies are not related to the condition. Testosterone supplements wouldn't have an effect and wouldn't reverse the consequences.
Dr. Forsberg went back to his computer and looked at the data on the aging men in the study.
The doctor said that he had the data in a few hours. Men with loss of Y in a large proportion of their blood cells were only able to survive half as long.
He said that he could imagine his surprise. Everything was redid.
He published a paper in the journal Nature Genetics in which he reported that increased death rates and cancer diagnoses were linked to a loss of the Y chromosomes in blood cells.
He started a company to test men for loss of Y.
Similar analyses were published by other researchers. There are associations between loss of the Y chromosome in blood cells and heart disease, as well as shortened life spans and diseases related to age.
Kenneth Walsh was the director of the Hematovascular Biology Center at the University of Virginia. Dr. Walsh became interested in the loss of Y chromosomes because of his work on a different type of genetic loss that happens with aging: an increase in cancer genes in blood cells called CHIP. People with CHIP have a higher risk of cardiovascular disease and cancer.
The director of preventive cardiology at Massachusetts General Hospital and others formed a company to develop a cost-effective test for CHIP and to study treatments to prevent its consequences.
CHIPs are only a small part of the genetic alterations that happen with age.
He wanted to know what the rest of the pie looked like. He wondered if there was a correlation between the loss of Y in blood cells and diseases. He studied with mice.
The mice looked fine at first, but then they aged poorly. Their life spans were shortened and they developed scar tissue in their hearts, kidneys and lungs, a type that is not the result of a heart attack and whose cause is not understood. Mental abilities of the animals were diminished.
Dr. Walsh looked at the data from the UK Biobank.
During a seven-year follow up, men with mosaic loss of Y had a 41 percent increased risk of dying from any cause and a 31 percent increased chance of dying from cardiovascular disease. The risk increases when cells lose Y chromosomes.
The work raises questions about women. They have two X chromosomes. What do you think about women with Turner Syndrome? All their cells are the same size as a random group of blood cells in men who lose their Y.
As women age, they can lose an X, but not as much as men.
Turner Syndrome is not the same. Men who have lost their Y chromosomes have the same health risks as women with the condition. Women with two X's have longer life spans.
It's too early to say what men should do to protect themselves from losing their Y chromosomes or alleviate the consequences.
Those in Dr. Walsh's group were able to protect the hearts of the mice without Y chromosomes by blocking TGF-beta.
Stephen Chanock is the director of the division of cancer epidemiology and genetics at the National Cancer Institute. There is no evidence that drugs to block TGF-beta will work in men who have lost their Y.
There isn't much point in testing men for loss of Y at the moment.
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