Men tend to lose the Y chromosome from their cells as they age. But because the Y bears few genes other than for male determination, it was thought this loss would not affect health.
New techniques to detect Y chromosome genes show frequent loss of the Y in tissues of older men. The increase with age is clear: 40% of 60-year-old men show loss of Y, but 57% of 90-year-olds. Environmental factors such as smoking and exposure to carcinogens also play a role.
Loss of Y occurs only in some cells, and their descendants never get it back. This creates a mosaic of cells with and without a Y in the body. Y-less cells grow faster than normal cells in culture, suggesting they may have an advantage in the body – and in tumours.
The Y chromosome is particularly prone to mistakes during cell division – it can be left behind in a little bag of membrane that gets lost. So we would expect that tissues with rapidly dividing cells would suffer more from loss of Y.
The human Y is an odd little chromosome, bearing only 51 protein-coding genes (not counting multiple copies), compared with the thousands on other chromosomes. It plays crucial roles in sex determination and sperm function, but was not thought to do much else.
Despite its apparent uselessness to most cells in the body, evidence is accumulating that loss of Y is associated with severe health conditions, including cardiovascular and neurodegenerative diseases and cancer.
Loss of Y frequency in kidney cells is associated with kidney disease.
Several studies now show a relationship between loss of Y and cardiac disease. For instance, a very large German study found men over 60 with high frequencies of loss of Y had an increased risk of heart attacks.
Loss of Y has also been linked to death from COVID, which might explain the sex difference in mortality. A tenfold higher frequency of loss of Y has been found in Alzheimer’s disease patients.
Several studies have documented associations of loss of Y with various cancers in men. It is also associated with a poorer outcome for those who do have cancer.
PS: The DNA of the human Y was only fully sequenced a couple of years ago – so in time we may track down how particular genes cause these negative health effects.
(The full gap free Y DNA sequence was by T2T Consortium in mid 2023, which was the final human chromosome to be fully sequenced)
New techniques to detect Y chromosome genes show frequent loss of the Y in tissues of older men. The increase with age is clear: 40% of 60-year-old men show loss of Y, but 57% of 90-year-olds. Environmental factors such as smoking and exposure to carcinogens also play a role.
Loss of Y occurs only in some cells, and their descendants never get it back. This creates a mosaic of cells with and without a Y in the body. Y-less cells grow faster than normal cells in culture, suggesting they may have an advantage in the body – and in tumours.
The Y chromosome is particularly prone to mistakes during cell division – it can be left behind in a little bag of membrane that gets lost. So we would expect that tissues with rapidly dividing cells would suffer more from loss of Y.
The human Y is an odd little chromosome, bearing only 51 protein-coding genes (not counting multiple copies), compared with the thousands on other chromosomes. It plays crucial roles in sex determination and sperm function, but was not thought to do much else.
Despite its apparent uselessness to most cells in the body, evidence is accumulating that loss of Y is associated with severe health conditions, including cardiovascular and neurodegenerative diseases and cancer.
Loss of Y frequency in kidney cells is associated with kidney disease.
Several studies now show a relationship between loss of Y and cardiac disease. For instance, a very large German study found men over 60 with high frequencies of loss of Y had an increased risk of heart attacks.
Loss of Y has also been linked to death from COVID, which might explain the sex difference in mortality. A tenfold higher frequency of loss of Y has been found in Alzheimer’s disease patients.
Several studies have documented associations of loss of Y with various cancers in men. It is also associated with a poorer outcome for those who do have cancer.
PS: The DNA of the human Y was only fully sequenced a couple of years ago – so in time we may track down how particular genes cause these negative health effects.
(The full gap free Y DNA sequence was by T2T Consortium in mid 2023, which was the final human chromosome to be fully sequenced)
