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2022-07-20| R&D

Geneticists Find Loss of Y Chromosome in Aging Males Increases Risk of Heart Failure

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The Y chromosome is unique to male individuals in mammals and its functions are not fully understood. It carries only about 70 genes, less than one-tenth the size of the X chromosome, and cells can still survive and reproduce without a Y chromosome. Many studies have pointed out that males gradually lose their Y chromosomes from their cells during the aging process. The previous school of thought suggested that the Y chromosome carries a large number of repetitive DNA fragments, which are useless junk DNA, and therefore would not cause much trouble despite the loss of the Y chromosome, but a new study published in the journal Science disproves this argument.

The genetics team at the University of Cambridge conducted experiments on male mice to remove the Y chromosome and found that these mice died earlier than normal mice, and further noted that mice lacking the Y chromosome showed more signs of cardiac fibrosis and increased risk of death from heart failure.

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Male Mice Lacking Y Chromosome Are Prone to Cardiac Fibrosis

 

To understand how the loss of the Y chromosome affects the health conditions of male mice, the team used CRISPR-Cas9 gene editing to delete the Y chromosome from bone marrow cells and transplanted the modified cells into 38 young male mice that have had their bone marrow removed. Approximately 49-81% of the bone marrow cells in these transplanted mice lacked the Y chromosome, which is similar to the percentage of male humans with Y chromosome loss. The 37 mice in the control group also received bone marrow transplants, but the white blood cells retained the intact Y chromosome.

The team then followed the two groups of test animals for two years and found that only about 40% of mice in the experimental group with Y chromosome deficiency survived beyond 600 days after transplantation, while 60% of mice in the control group survived beyond 600 days, indicating that mice with Y chromosome deficiency would have a shorter life span. The team found that it was caused by macrophages in Y chromosome deficient mice that induced the proliferation of tough connective tissue, causing cardiac fibrosis and impairing blood circulation.

 

Deficiency of Y Chromosome Increases the Risk of Cardiovascular Disease in Humans

 

After obtaining theoretical evidence from the mouse model, the team also wanted to investigate the effects of losing the Y chromosome in humans. They collected DNA and medical data from more than 15,000 men in the UK Biobank and found that men with at least 40% loss of the Y chromosome in their white blood cells had a 31% higher chance of dying from cardiovascular and circulatory diseases, the most common one being heart failure.

The study, based on the results of animal models and human biological databases, suggests that although the Y chromosome carries less DNA, the loss of the Y chromosome in male individuals during the aging process increases the risk of heart disease and other aging-related diseases such as cancers and Alzheimer’s disease, which may be one of the many factors that contribute to the shorter average life expectancy of men compared to women.

 

Written by Kathy Huang, Translated by Richard

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