Why Men Die Earlier


A study published in Science found that the loss of the Y chromosome, which occurs naturally in many men as they age, can cause heart scarring and premature death.

Scientists have known for half a century that the Y chromosome can disintegrate over time, but they weren’t sure if the downstream consequences mattered. 

New research from the University of Virginia suggests that the consequences of a degrading Y chromosome definitely matter. When researchers genetically removed the Y chromosome from the white blood cells of mice, they found that:

  • The mice died earlier and with more cardiac fibrosis.
  • Heart function was restored by treating the mice with a drug that blocks heart scarring. 

To tie these findings to human men, the researchers analyzed genetic data from the UK Biobank (223k men) and found that:

  • Men with a mosaic loss of the Y chromosome had a 41% increased risk of dying from any cause during a 7-year follow-up, and a 31% increased risk of dying from cardiovascular disease. 
  • These men were two to three times more likely to die of congestive heart failure or heart disease.
  • As Y chromosome loss increased, so did the risk of dying from CVD. 

A drug that may help counter the Y loss-associated heart scarring is already on the market. FDA-approved pirfenidone is used to treat idiopathic pulmonary fibrosis, a form of lung scarring, and has undergone trials for heart failure. The study’s authors note that men with Y loss may have a “superior response to this class of therapeutic agents,” although this has not been tested directly yet. 

The Takeaway

These findings demonstrate that Y chromosome loss can directly contribute to age-related heart disease through tissue scarring, and suggest that targeting the effects of Y chromosome loss could help men live longer, healthier lives. 

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