Men lose Y chromosomes from their cells as they age. But since the Y accommodates few genes apart from male determination, it was thought that this loss wouldn't affect health.
But Evidence has been mounting over the past few years That when individuals with a Y chromosome lose it, the loss is linked to serious diseases throughout the body, shortening lifespan.
Loss of Y in older men
New technique for detecting Y chromosome genes reveals frequent lack of Y in tissues of older men. gave Increase with age The obvious: 40 percent of 60-year-old men show Y deficiency, but 57 percent of 90-year-old men. Environmental aspects akin to smoking and exposure to carcinogens also play a task.
The lack of Y occurs only in some cells, and their offspring never regain it. It forms a mosaic of cells with and without Y within the body. Y-deficient cells grow faster than normal cells in culture, suggesting they might have a bonus within the body and in tumors.
The Y chromosome is especially vulnerable to errors during cell division – it may be left in a small sac within the membrane that gets lost. We would subsequently expect tissues with rapidly dividing cells to be more affected by Y loss.
Why does the lack of a defective Y gene matter?
The human Y is an oddly small chromosome, containing only 51 protein-coding genes (not counting multiple copies) in comparison with hundreds on other chromosomes. It plays a vital role in sex determination and sperm function, but was not thought to do way more.
When cells are cultured within the laboratory, the Y chromosome is usually lost. It is the one chromosome that might be lost without killing the cell. This suggests that no specific functions encoded by Y genes are essential for cellular growth and performance.
In fact, the boys of Some marsupial species Y chromosomes pair up early of their development, and evolution appears to be accelerating together with it. In mammals, Y has been degenerate for 150 million years and has already been lost and mutated in some rodents.
So the lack of Y in body tissues at the tip of life should actually not be dramatic.
Association of Y loss with health problems
Despite its apparent uselessness for many cells within the body, evidence is accumulating that lack of Y is linked to serious health conditions, including cardiovascular and neurological diseases and cancer.
Associated with lack of Y frequency in kidney cells Kidney disease.
Several studies now show a link between Y loss and heart disease. For example, A great German study Men over 60 years of age were found to have an increased risk of heart attack in those with a high frequency of Y deficiency.
Loss of Y has also been linked to deaths from COVID, which can explain this. Sex differences in mortality. There has been a tenfold higher frequency of Y loss. Found in Alzheimer's patients..
Several studies have documented the association of loss with Y. Various cancers in men. It can also be related to poor outcomes for individuals who have cancer. Among other chromosomal abnormalities, Y loss is common in cancer cells themselves.
Does Y deficiency cause morbidity and mortality in older men?
Finding out what causes the links between lack of Y and health problems. They could also be because health problems cause the lack of Y, or perhaps a 3rd factor may cause each.
Even strong associations cannot prove causation. An association with kidney or heart disease may result from rapid cell division during organ repair, for instance.
Cancer associations may reflect a genetic predisposition to genome instability. Indeed, genome-wide association studies show that the Y frequency loss is approx. One-third geneticwhich incorporates 150 identified genes which are widely involved in cell cycle regulation and cancer susceptibility.
nevertheless, A mouse study Indicates a direct effect. Researchers transplanted Y-deficient blood cells into irradiated mice, which then showed an increased frequency of age-related pathologies, including impaired heart function and subsequent heart failure.
Similarly, lack of Y from cancer cells directly affects cell growth and malignancy, Possibly driving eye melanomawhich occurs more regularly in men.
The role of Y in body cells
The clinical implications of Y loss suggest that the Y chromosome has vital functions within the body's cells. But given what number of genes it hosts, how?
The male-determining SRY gene found on the Y is widely expressed within the body. But the one effect of its activity within the brain is to cause Parkinson's disease. And the 4 genes needed to make sperm are energetic only within the testes.
But lots of the other 46 genes on the Y are widely expressed and play essential functions in gene activity and regulation. There are several known cancer suppressors.
All of those genes have copies on the X chromosome, so each women and men have two copies. It could also be that Y-deficient cells lack the second copy to cause an anomaly.
In addition to those protein-coding genes, the Y accommodates many non-coding genes. These are transcribed into RNA molecules, but never translated into proteins. At least Some of these non-coding genes It seems to manage the function of other genes.
This may explain why the Y chromosome can. Affects activity. Genes on many other chromosomes. Y deficiency affects the expression of certain genes in cells that make blood cells, in addition to others that regulate immune function. It may not directly affect blood cell types and heart function differences.
The DNA of the human Y was only fully sequenced a couple of years ago – so over time we may give you the option to determine how specific genes cause these negative health effects.