The Who’s, What’s, and “Y”s: Y Sex Chromosome Loss and Methylation for Analysis in Male Aging and Mortality and Forensic Science Applications

The Y chromosome plays a crucial role in understanding the overall landscape of male health. Incorporating the Y chromosome into genomic and epigenomic research may elucidate the male-specific mechanisms behind aging and the pathogenesis of certain conditions, both acute and chronic. Present epigenetic research focuses on the effects of modifications like methylation on autosomal chromosomes. However, little research has been conducted to further these investigations in sex chromosomes, especially the Y chromosome. Epigenetic analyses can identify age-associated CpG sites that may offer potential biomarkers for age estimation and disease risk assessment, among others. This review emphasizes interdisciplinary efforts that have been made in the construction of an assembly and the application of “epigenetic clocks” to the Y chromosome. The studies reviewed here examined the effects of aging on genes such as NLGN4Y, DDX3Y, and TBL1Y, and on male-specific health disparities and disease etiologies, as well as the potential for the use of these genes to assess the diagnostic and age algorithmic potential of Y-specific genes.