The Impact of Y Chromosome Loss on Men’s Health
As men age, they tend to lose the Y chromosome from their cells, a phenomenon that was previously thought to have minimal impact on health due to the Y chromosome’s limited gene content related to male determination. However, recent evidence has revealed that the loss of the Y chromosome is associated with various serious diseases and can contribute to a shorter lifespan.
Y Chromosome Loss in Older Men
Recent advancements in detecting Y chromosome genes have shown that the loss of the Y chromosome in tissues is prevalent among older men. Studies have indicated that the frequency of Y chromosome loss increases with age, with 40% of 60-year-old men and 57% of 90-year-olds exhibiting this loss. Environmental factors such as smoking and exposure to carcinogens have also been linked to Y chromosome loss.
The loss of the Y chromosome occurs in specific cells and their descendants do not regain it, resulting in a mosaic of cells with and without the Y chromosome in the body. Research suggests that Y-less cells have a growth advantage, particularly in tumors, as they proliferate faster than normal cells.
Significance of Y Chromosome Loss
Despite its limited gene content, the Y chromosome has shown to have significant implications when lost from cells. While it was previously believed to have minimal impact, studies have demonstrated that the loss of the Y chromosome is associated with severe health conditions such as cardiovascular diseases, neurodegenerative diseases, and cancer.
Notably, the frequency of Y chromosome loss in kidney cells has been linked to kidney disease, and studies have shown a correlation between the loss of Y chromosome and cardiac diseases, with men over 60 exhibiting higher risks of heart attacks.
Y Chromosome Loss and Disease
Research has also indicated associations between Y chromosome loss and conditions like Alzheimer’s disease, COVID mortality, and various cancers in men. The presence of Y chromosome loss in cancer cells has been linked to poorer outcomes and increased malignancy.
While determining the exact causal relationship between Y chromosome loss and health problems is challenging, studies suggest a genetic predisposition for genome instability and dysregulation of gene activity and regulation in Y-less cells.
Insights into Y Chromosome Function
Despite hosting a relatively small number of genes, the Y chromosome plays essential roles in gene activity and regulation, including acting as cancer suppressors. The presence of non-coding genes on the Y chromosome that control the function of other genes may explain its impact on gene activity across multiple chromosomes.
Recent advancements in the sequencing of the human Y chromosome may provide further insights into the specific genes responsible for the negative health effects associated with Y chromosome loss.
By: Jenny Graves, Distinguished Professor of Genetics and Vice Chancellor’s Fellow at La Trobe University
This article is a revised version of the original article published on The Conversation under a Creative Commons license. For more information, please refer to the original article.

