While most women have two X chromosomes in their cells, men usually only have one of them – and an additional Y chromosome. However, this Y chromosome can be lost over the course of life as a result of age-related gene mutations during cell division. The health consequences are manifold, explained the science journalist Michael Lange in an interview with Dlf: Heart diseases then occur more frequently, as do cancer and Alzheimer’s. This may be one reason why men die earlier than women on average.
Why do many men lose their Y chromosome over the course of their lives?
The male Y chromosome is by far the smallest human chromosome. There are only a few genes on it that ensure that an embryo becomes male. If the Y chromosome is missing, a female embryo develops. Later in a man’s life, the Y chromosome is often lost due to copying errors during cell division. A mosaic of body cells with an Y chromosome and cells without an Y chromosome develops.
The smaller a chromosome, the greater the risk that both daughter cells will not have an Y after cell division. Loss of the Y during life is the most common mutation in humans. This has been well studied in white blood cells. Other cells are likely to be affected as well. Especially those that divide often, such as skin cells or cells of the intestinal epithelium.
How does the loss of the Y chromosome affect health?
The loss of the upsilon chromosome has long been recognized as a possible main reason why men live an average of five to six years less than women. This new research, now using data from the UK Biobank in the UK, shows that many white blood cells in older men often no longer have the Y chromosome. Around 20 percent of the cells are affected in 60-year-old men, and even 40 percent in 70-year-old men. The results now available prove a clear connection between the loss of the Y chromosome and cardiovascular diseases. The risk of tumor diseases and Alzheimer’s disease is also increased.
What happens in blood cells where the Y chromosome is missing?
To study this, teams of scientists in the US and Sweden modified mice so that their blood cells lacked the upsilon chromosome. They did this by making targeted genetic changes using the Crispr/Cas gene scissors. When they examined the mice, they then discovered significant damage to the heart. Fibrosis was common. This means that harmful connective tissue formed – a kind of scar tissue that disrupts the function of the affected organ. As a result, the number of heart infections in particular is increasing.
The mouse experiments show that if the Y chromosome is missing, the animals activate a specific molecular signaling pathway. The growth factor TGF-Beta 1 plays a key role. This leads to fibrosis and increases the risk of cardiovascular disease.
Are there therapeutic approaches to prevent such heart damage?
To do this, it would first have to be examined whether the blood cells of a man are missing the Y chromosome. That’s relatively easy. In men who lack the Y, a disease-preventive treatment would then be conceivable. For example, with drugs that fight fibrosis. The active ingredient pirfenidone could be useful here. It is approved and used against pulmonary fibrosis. A monoclonal antibody that specifically blocks the harmful signaling pathway was also tested on mice. But it will certainly be a long time before therapy can be used in humans.
Is there a way to prevent the loss of the Y chromosome?
The loss of the Y is a result of the natural aging process. Cell division becomes more imprecise with age, and errors occur. That can’t be prevented. Unless it succeeds in directly influencing the aging process. In principle, this is possible, for example through a healthy lifestyle: sufficient exercise, healthy nutrition, no smoking.
If the Y chromosome is so important, why do women do so well without it?
This question has not yet been clarified. Females have a second X chromosome instead of the Y chromosome. It serves as a backup in case of harmful mutations. Apparently this works quite well. The lack of the Y chromosome in women does not appear to have any harmful effect. Because women live longer and suffer less frequently from age-related cardiovascular diseases. It is also possible without an Y chromosome.