What Y chromosome's unexpected impact on aging and disease in men

LOY in human male cells was first identified over 60 years ago but gained significant attention only recently. Initially thought to have little impact beyond sex differentiation and sperm production, LOY is now recognized as a common somatic mutation with broad effects.

Recent research has revealed that LOY originates from mitotic errors, often involving the trapping of the Y chromosome in micronuclei, which eventually disintegrate. Research since 2014 has linked LOY to increased risks of mortality, cancer, and Alzheimer’s disease, with environmental factors like smoking contributing to its occurrence. Unlike other mutations, LOY is always a mosaic event and cannot be inherited.

Recent advances in Y chromosome sequencing have revitalized research, enhancing our understanding of LOY’s role in health and disease. Moreover, LOY is increasingly viewed as a marker of genome instability and a biological indicator of environmental stress