A novel epigenetic clock for rhesus macaques unveils an association between early life adversity and epigenetic age acceleration

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Because DNA methylation changes reliably with age, machine learning models called epigenetic clocks can estimate an individual's age based on their DNA methylation profile. This epigenetic measure of age can deviate from one's true age, and the difference between the epigenetic age and true age, known as epigenetic age acceleration (EAA), has been found to directly correlate with morbidity and mortality in adults. Emerging evidence suggests that EAA is also associated with aberrant health outcomes in children, making epigenetic clocks useful tools for studying aging and development. We developed two highly accurate epigenetic clocks for the rhesus macaque, utilizing 1,008 blood samples from 690 macaques between 2 days and 23.4 years of age with diverse genetic backgrounds and exposure to environmental conditions. The first clock, which is trained on all samples, achieves a Pearson correlation between true age and predicted age of 0.983 and median absolute error of 0.210 years. To study phenotypes during development, the second clock is optimized for macaques younger than 6 years and achieves a Pearson correlation of 0.974 and a median absolute error of 0.148 years. Using the latter clock, we investigated whether epigenetic aging is affected by early life adversity in the form of infant maltreatment. Our data suggests that maltreatment and increased hair cortisol levels are associated with epigenetic age acceleration right after the period of maltreatment.

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