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XY chromosome
Men tend to lose the Y chromosome from their cells as they age. But because Y has few genes other than those related to male sex determination, it was thought that this loss would not affect health.
Over the past few years, evidence has been accumulating that when people who have a Y chromosome lose it, this loss is associated with serious illnesses throughout the body, contributing to a shorter life expectancy.
New techniques to detect genes on the Y chromosome show a frequent loss of the Y in the tissues of older men. The increase with age is evident: 40% of 60-year-old men have loss of the Y, but by the age of 90 it is 57%.
Furthermore, environmental factors how smoking and exposure to carcinogens also play a role in the loss of this chromosome, explains the genetics professor Jenny Gravesfrom La Trobe University, in an article in .
Lost Y occurs only in some cellsand their descendants never recover it. This creates a mosaic of cells with and without Y in the organism. Cells lacking Y grow faster than normal cells in culture, suggesting that may have an advantage in the body – and in tumors.
The Y chromosome is particularly error-prone during cell division – it can be trapped in a small membrane envelope that is lost. Therefore, it would be expected that the tissues with rapidly dividing cells suffered more with the loss of Y.
Why does the loss of a gene-poor Y matter?
The human Y is a small and peculiar chromosomecontaining just 51 protein-coding genes, compared to the thousands present on other chromosomes. Performs Crucial roles in sex determination and sperm function, but it was thought to not do much else.
The Y chromosome is often lost when cells are grown in the laboratory. And the the only chromosome that can be lost without killing the cellwhich suggests that no specific functions required encoded by Y genes for cell growth and function.
In fact, males of some marsupial species discard the Y chromosome early in their development, and evolution appears to be rapidly progressing. do without it. In mammals, Y has degraded over 150 million years and has already been lost and replaced in some rodents. Therefore, the loss of Y in body tissues at the end of life It certainly shouldn’t be a drama.
Despite its apparent uselessness to most of the body’s cells, evidence is accumulating that loss of Y is associated with serious health conditions, including cardiovascular and neurodegenerative diseases, and cancer.
The frequency of Y loss in kidney cells is also associated with kidney disease, and several studies now show a relationship between Y loss and heart disease. For example, an extensive German study concluded that men over 60 years of age and with high frequencies of Y loss had an increased risk of myocardial infarction.
The loss of Y was also associated with death from COVIDwhich could explain the difference in mortality between sexes. A tenfold higher frequency of Y loss was found in patients with Alzheimer’s disease.
Several studies have documented associations of Y loss with different types of cancer in menand a more unfavorable prognosis for those with cancer. Loss of the Y is common in cancer cells themselves, among other chromosomal abnormalities.
Does it cause illness and mortality in older men?
Understanding what causes the links between Y loss and health problems is difficult. They may occur because health problems cause the loss of the Y, or perhaps a third factor may cause both.
Even strong associations may not prove causality. The association with kidney or heart disease could result from rapid cell division during organ repair, for example.
Associations with cancer may reflect a genetic predisposition for genomic instability. Indeed, genome-wide association studies show that the frequency of Y loss is about 1/3 geneticsinvolving 150 identified genes mainly involved in the regulation of the cell cycle and susceptibility to cancer.
However, a study conducted on mice, published in 2022 in the journal Science, points to a direct effect. The researchers transplanted Y-deficient blood cells into irradiated mice, which then showed increased frequencies of pathologies age-related symptoms, including lower heart function and subsequent heart failure.
Likewise, the loss of Y in cancer cells seems to affect directly cell growth and malignancy, possibly driving ocular melanoma, which is more common in men.
Role of Y in body cells
The clinical effects of Y loss suggest that the Y chromosome has important functions in the body’s cells. But given how few genes it harbors, how?
Or SRY gene masculine determination found in Y is expressed widely in the body. But the only effect attributed to its activity in the brain is the complicity in causing Parkinson’s disease. And four genes essential for producing sperm are active only in the testicles.
But among the other 46 genes on the Y, several are widely expressed and have essential functions in gene activity and regulation. Several are known cancer suppressants.
These genes all have copies on the X chromosomeso both men and women have two copies. It may be that the absence of a second copy in cells without Y causes some type of dysregulation.
In addition to these protein-coding genes, Y contains many non-coding genes. These are transcribed into RNA molecules but never translated into proteins. At least some of these non-coding genes appear control the function of other genes.
This could explain why the Y chromosome can affect the activity of genes on other chromosomes. The loss of the Y affects the expression of some genes in cells that produce blood cells, as well as others that regulate immune function. It may also indirectly affect the differentiation of blood cell types and heart function.
Human Y DNA was only fully sequenced a few years ago. So, over time, we may be able to discover how specific genes cause these negative health effects, concludes Jenny Graves.
