[Y chromosome loss in hematopoietic cells and its clinical implications]

Somatic mosaicism is emerging as a fundamental feature of human aging. Among its most common manifestations in men is acquired loss of the Y chromosome (LOY) in the hematopoietic system, which is most readily detected in blood cells. Although this has long been regarded as a largely incidental consequence of aging, the view is now changing. Epidemiologic studies, human genetic analyses, and experimental models have linked LOY to clonal hematopoiesis, immune dysregulation, chronic inflammation, impaired tissue repair, cardiovascular disease, cancer, and neurodegenerative disorders. Although the human Y chromosome has undergone extensive gene loss during evolution, it has retained genes with functions beyond sex determination and spermatogenesis, including genes expressed in hematopoietic and immune cells. Thus, LOY is not merely a numerical chromosomal abnormality; it may mark, and in some contexts drive, altered cellular states with systemic consequences. In this review, I discuss the evolutionary and biological features of the Y chromosome, summarize current evidence connecting LOY with human disease, and consider how LOY reframes our understanding of aging, immunity, and sex-specific disease susceptibility in men.