According to the medical researcher, men lose individual Y chromosomes in their cells with advancing age Kenneth Walsh from the University of Virginia has been known for a long time and is anything but rare. Between 40 and 50 percent of all men by the age of 70 would have such a mutation. According to the medical researcher, this is the most common cell mutation in males.
Men are affected differently
The number of those affected increases with age, but also through behavior that is harmful to health, such as smoking. You have a mosaic mixture of blood cells, some with the Y chromosome and some not. Walsh explains to science.ORF.at: “Some men only lack the Y chromosome in a few cells, others hardly have any that contain it.” The medical researcher knows of a case in which over 80 percent of the blood stem cells have a man did not have a Y chromosome.
For a long time, this was not seen as a major problem, says Walsh. He explains: “For some time it was assumed that the Y chromosome had hardly any other function after the development of the male genitalia.” This is also shown by the fact that the chromosome is commonly known among experts as the “genetic wasteland”.
Signs of aging or triggers of illness?
However, earlier studies have shown that the mosaic loss of Y chromosomes, also known as mLOY (mosaic loss of chromosome Y), could be related to diseases in some way. According to Walsh, well-known examples include leukemia, cancer, Alzheimer’s disease and heart problems.
So far, however, it has been unclear to what extent mLOY actually affects the health of the men concerned. Walsh: “People did not know whether the missing Y chromosomes, like gray hair, are a normal symptom of aging and only coincidentally accompany the diseases, or whether they have something to do directly with the development of these diseases.”
Mice lacking the Y chromosome
Walsh therefore made it his task, together with international researchers, to find out more about the connection between mLOY and common heart problems.
To do this, the team examined mice in the laboratory. The Y chromosomes were previously removed from almost 65 percent of the blood stem cells in the animals. Walsh: “We were able to examine more precisely than ever whether the missing chromosomes actually lead to heart problems or whether they are just a side effect of aging.” result Walsh and the research team are currently presenting in the journal “Science”.
risk of heart failure
The experiment showed that the mice affected by mLOY were significantly more susceptible to Herzfibrosen, i.e. scarring of the heart tissue. As a result, the animals also had a higher risk of heart failure.
To check whether the findings from the laboratory can also be observed in humans, the team examined data from the UK Biobank. The result: “Men who have fewer Y chromosomes as they age not only die earlier on average, they are also more likely to develop heart problems at some point,” says Walsh. A loss of Y chromosomes is also a key reason why the life expectancy of men lags behind that of women on a global average.
No genetic wasteland
One thing is clear from the results of the study: “The Y chromosome is not a genetic wasteland. It still has a function as we age,” Walsh says. An important finding, also according to the cardiologist Andreas Zeiher from the University Hospital in Frankfurt. He was not involved in the study, but has one that was also published in the journal Science Comment co-authored with the results.
Zeiher: “Very little is known about the function of the Y chromosome other than determining sex. All the more surprising is the well-documented finding that the loss of the Y chromosome in animal models is associated with connective tissue remodeling in the aging heart.”
The cardiologist also explains: “The loss of the Y chromosome as a risk factor for men to die from cardiovascular disease is comparable to the classic risk factors diabetes or increased blood lipids, but via a completely different mechanism.”
Antibodies could dampen scarring
The results from the animal experiment could also contribute to the development of new drugs. Certain immune cells in the blood (macrophages), which develop from blood stem cells and lack the Y chromosome, promoted scarring by activating a growth factor in heart tissue, the team said.
But: The researchers were able to neutralize the growth factor with an antibody. The process of scarring was thus partially dampened. Walsh speculates that the antibodies could also prevent heart fibrosis in men. However, numerous studies are still needed before it can actually be used on humans.
Zeiher is also convinced of this: “Now it is necessary to clarify which risk factors contribute to the loss of the Y chromosome. Are these the same ones that promote cardiovascular disease?” Walsh’s study is the basis of many questions that need to be clarified in future studies, says the cardiologist.