The Mystery Of The Y Chromosome: The Silent Loss in Male DNA That Worries Scientists
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The loss of the Y chromosome in some of the body's cells is common in older men and may be associated with heart disease, cancer, neurodegenerative diseases, and a shorter life expectancy. New genetic technologies have made it possible to detect this alteration accurately and identify risk factors. Animal experiments suggest that the loss may have direct effects on health, possibly by altering gene regulation and the functioning of the immune system.
For a long time, it was believed that the Y chromosome, the chromosome that biologically differentiates men from women, had limited importance beyond determining male sex and sperm production.
It contains relatively few genes compared to other chromosomes. Furthermore, cells can survive even when they lose the Y chromosome, leading scientists to believe that this loss would not have major health consequences.
However, more recent research shows that many men begin to lose the Y chromosome in some of their cells as they age. This phenomenon is called mosaic loss of the Y chromosome. "Mosaic" means that some cells in the body retain the Y chromosome, while others have lost it.
Studies indicate that more than 40% of men over 70 years old have this blood alteration, and the frequency increases with age. Factors such as smoking, exposure to toxic substances, and certain genetic variations also increase the risk.
But how do scientists detect this loss? They use modern genetic analysis techniques. One of them is next-generation sequencing, which allows reading large amounts of DNA at the same time and identifying whether the genetic material of the Y chromosome is absent in some cells.
Another technique uses a chemical reaction called polymerase chain reaction, which amplifies specific regions of DNA to check whether certain genes of the Y chromosome are present or not. By comparing the amount of genetic material of the Y with other chromosomes, it is possible to estimate how many cells have lost this chromosome.
Researchers also analyzed large genetic databases of thousands of men. These studies identified about 150 genes scattered throughout the genome that influence the probability of losing the Y chromosome. Many of these genes are involved in the control of cell division. This suggests that the loss of the Y chromosome may occur during the process of cell multiplication, when the chromosome simply "gets left behind" and is not properly incorporated into the new cell.
Laboratory observations have shown that cells lacking the Y chromosome sometimes grow faster than normal cells. This can give them a competitive advantage within certain tissues, causing them to become more numerous over time. This accelerated growth may also help explain why the loss of the Y chromosome is frequently found in cancerous cells.
The clinical associations are concerning. Several studies show that men with a higher proportion of cells lacking the Y chromosome have an increased risk of cardiovascular disease, certain types of cancer, neurodegenerative diseases such as Alzheimer's, and even higher mortality from infections like COVID-19.
However, association does not necessarily mean causation. It may be that the loss of the Y chromosome directly contributes to these diseases, or it may simply be a sign of accelerated cellular aging.
To investigate whether the loss of the Y chromosome can directly cause health problems, researchers conducted experiments with mice. They transplanted blood cells lacking the Y chromosome into animals whose own blood cells had been destroyed by radiation.
These mice developed more age-related problems, including worsening heart function. This result suggests that the loss of the Y chromosome may have real biological effects and not just be a statistical marker.
Although the Y chromosome has few genes, many of them participate in the regulation of other genes in the body. Some help control the immune system and cell growth. Because these genes have similar copies on the X chromosome, males typically have one version on the Y and another on the X.
When the Y chromosome is lost, the cell is left with only one copy, which can alter the balance of gene activity. Furthermore, the Y chromosome contains regions that produce regulatory molecules that influence the functioning of other genes. Future research should clarify more precisely how this loss contributes to disease.
READ MORE:
Mosaic loss of the Y chromosome and men's health
Maki Fukami, and Mami Miyado
Reproductive Medicine and Biology. Volume21, Issue1, January/December 2022, e12445
Abstract:
Although Y chromosomal genes are involved in male sex development, spermatogenesis, and height growth, these genes play no role in the survival or mitosis of somatic cells. Therefore, somatic cells lacking the Y chromosome can stay and proliferate in the body. Several molecular technologies, including next-generation sequencing and multiplex PCR-based assays, are used to detect mosaic loss of the Y chromosome (mLOY) in the blood of men. Accumulating evidence suggests that mLOY represents the most common acquired chromosomal alteration in humans, affecting >40% of men over 70 years of age. Advanced age, tobacco smoking, and some SNPs in cell cycle genes are known to increase the frequency of mLOY. The developmental process of mLOY in elderly men remains to be clarified, but it possibly reflects recurrent mitotic elimination of Y chromosomes or clonal expansion of 45,X cell lineages. In rare cases, mLOY also occurs in young men and fetuses. MLOY has been associated with early death, cancers, and other disorders in elderly men, infertility in reproductive-aged men, and developmental defects in children. Y chromosomes in men can be lost at every life stage and Y chromosomal loss is associated with various health problems.
The Conversation
Men lose their Y chromosome as they age. Scientists thought it didn’t matter – but now we’re learning more
Published: February 13, 2026 1.52am CET
Jenny Graves
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