Loss of chromosome Y (LOY) in blood cells is associated with increased risk for disease and mortality in aging men

Abstract

Recent discoveries have shown that harboring cells without the Y chromosome in the peripheral blood is associated with increased risk for all-cause mortality and disease such as different forms of cancer, Alzheimer's disease, as well as other conditions in aging men. In the entire world, the life expectancy of men is shorter compared to women, a sex difference that has been known for centuries, but the underlying mechanism(s) are not well understood. As a male-specific genetic risk factor, an increased risk for pathology and mortality associated with mosaic loss of chromosome Y (LOY) in blood cells could help to explain that men on average live shorter lives compared to women. This review primarily focuses on observed associations between LOY in blood and various diseases in aging men. Other topics covered are known risk factors for LOY, methods to detect LOY, and a discussion regarding mechanisms such as immunosurveillance, that could possibly explain how an acquired mutation in blood cells can be associated with disease processes in other organs.

Fig. 1

Men live on average shorter lives compared to women. Each dot shows data from one nation or human population. The red line represents the observed difference in lifespan and the black line represents a null hypothesis with no difference in longevity between the sexes. The dotted lines mark the male and female life expectancies globally and in the European Union (EU). Data from The World Factbook 2013 on male and female life expectancy at birth in different human populations in 2013 (https://www.cia.gov/library/publications/the-world-factbook/)