Sperm epigenetics and aging

Timothy G. Jenkins, Kenneth I. Aston, Douglas T. Carrell


Advanced paternal age has very real consequences in fertility, embryogenesis, and even offspring health. Specifically, advanced paternal age has been linked to delayed time to pregnancy and in some studies even appears to be linked to a decreased likelihood of achieving a pregnancy. Epidemiological and animal model evidence also suggests that the offspring of older fathers are at an elevated risk for neuropsychiatric disease. For these reasons it is essential that we have a comprehensive understanding of what actually occurs in the gametes of the aging male. Available data suggest that there are very clear patterns of aging in the sperm epigenome that can be directly detected in DNA methylation patterns. Importantly, these alterations are so consistent that a predictive model has been successfully generated to predict an individual’s age based only on sperm DNA methylation signatures. Because this metric is the most direct way to detect aging in sperm, it is logical that these signatures may offer predictive value for the offspring abnormalities that are also correlated with advanced paternal age and as such may offer a unique opportunity to generate diagnostic tools that can identify personalized risks for each couple hoping to achieve a pregnancy. While a great deal of work still needs to be performed to understand the real diagnostic utility of sperm epigenetic marks, the potential is real and warrants further investigation particularly in the context of advanced paternal age.