Men lose their Y chromosome as they age: scientists warn of danger

Scientists have found that with age, many men lose the Y chromosome in some of their cells, and this phenomenon is associated with increased risks of diseases and reduced life expectancy. New research shows that chromosome loss is much more dangerous than previously thought.

Research over the past few years shows that the loss of the Y chromosome causes serious health problems throughout the body and may contribute to a shortened lifespan.

How common is Y chromosome loss?

Loss of the Y chromosome, recent research has shown, is widespread among older men. This problem affects approximately 40% of men at the age of 60, and by the age of 90 this figure increases to 57%. Exposure to environmental factors such as smoking and exposure to carcinogens may increase the likelihood of this change.

Loss of the Y chromosome does not occur in all cells. Over time, a mix of normal and degraded cells is obtained. This was called mosaicism. Once a cell loses its Y chromosome, all future copies of it also lose it. Laboratory studies show that cells without a Y chromosome can grow faster than normal cells, which may give them an advantage in tissues and even tumors.

The Y chromosome is especially vulnerable during cell division. It may be accidentally removed and remain in a small membranous structure, which is subsequently discarded. Because of this, in tissues where cells divide rapidly, loss of the Y chromosome occurs more often.

Why is the small chromosome important

class=»notranslate»>__GTAG9__The human Y chromosome is unusual. It contains only 51 protein-coding genes (not counting multiple copies), in contrast to the thousands of genes found on other chromosomes. Its known functions include male sex determination and maintaining sperm production. For a long time it was believed that its functions were limited to this.

In laboratory conditions, cells can lose the Y chromosome and still survive, supporting the idea that it is not essential for basic cellular functions. In fact, some marsupials lose the Y chromosome early in development, and in mammals this chromosome has been decreasing in size for about 150 million years. In some rodents it even disappeared and was replaced by a new one.

Given this history, loss of the Y chromosome later in life was once thought to be minor.

The relationship between diseases and reduced life expectancy

Contrary to previous assumptions, growing evidence suggests that the loss of the Y chromosome is associated with serious diseases. Research has linked it to cardiovascular disease, neurodegenerative disorders and cancer.

For example, higher levels of Y chromosome loss in kidney cells are associated with kidney disease. Large population studies have also shown that men over 60 with more cells deficient in the Y chromosome are at greater risk of heart attacks.

Loss of the Y chromosome is associated with worse outcomes from COVID-19, which may help explain the higher death rate among men. It is also much more common in people with Alzheimer's disease. In addition, numerous studies show an association between Y chromosome loss and various types of cancer, as well as worse survival among affected patients. Cancer cells themselves often exhibit this chromosomal loss along with other abnormalities.

Cause or effect?

It remains challenging to determine whether the loss of the Y chromosome directly causes the disease or simply occurs simultaneously with it. In some cases, disease or tissue repair can lead to increased cell division, which can increase the likelihood of chromosome loss.

Genetic factors also appear to play a role. Research shows that about a third of the variation in Y chromosome loss is inherited and affects about 150 genes associated with cell cycle control and cancer risk.

However, experimental evidence points to a more direct effect. In one study, mice given Y chromosome-deficient blood cells developed more age-related diseases, including decreased heart function and eventually heart failure.

There are also indications that the loss of the Y chromosome may directly affect the behavior of cancer cells. In some cases, this can contribute to the growth and aggressiveness of tumors, including ocular melanoma, which is more common in men.

What is the function of the Y chromosome in the body?

The health consequences of Y chromosome loss suggest that it plays a broader role than previously thought. But how can a chromosome with so few genes have such a large impact?

One of the key genes, SRY, is active in many tissues of the body. Its known role in the brain includes involvement in Parkinson's disease. Four additional genes are active only in the testes and are required for sperm production.

In addition, many of the remaining genes on the Y chromosome are active in various tissues and help regulate gene expression. Some of them act as tumor suppressors. These genes also have counterparts on the X chromosome, meaning that both men and women usually have two copies. When cells lose the Y chromosome, they may have only one copy left, which can disrupt normal gene regulation.

The Y chromosome also contains many non-coding genes. They produce RNA molecules that are not converted into proteins but can influence the functioning of other genes. This may explain why the Y chromosome can influence the activity of many regions of the genome.

Loss of the Y chromosome has been shown to alter gene expression in cells of the hematopoietic system and cells involved in immune responses. It can also affect the development of blood cells and the functioning of the heart.

A look into the future

The complete sequence of the human Y chromosome has only recently been deciphered. As researchers continue to study her, they will likely learn more about how her genes influence health and disease, and why losing her can have such significant consequences.

Based on materials from sciencedaily

Xrust Men lose their Y chromosome as they age: scientists warn of the danger