Comparative age-related dynamics of primate brain epigenetics

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Our species is distinguished from other primates and mammals by our large brains and impressive cognitive abilities. Prolonged brain growth through development, along with a particularly long life, are essential to the emergence of human cognition, but may also lead to greater susceptibility to psychiatric and aging-related neurodegenerative disorders, like Alzheimer's disease. This project will characterize molecular changes in the brains of humans and other primates across the adult lifespan to identify features that distinguish the human pattern of brain development and aging. The results of this project will help pinpoint the genetic mechanisms underlying dynamic lifespan changes that are unique to human neurobiology and may improve our understanding of common medical conditions. The project will involve mentoring and building the analytical skills of trainees at different career stages (postdoctoral, graduate, undergraduate), and communicating results of this study to members of the public through accessible educational programming.The genetic and physiological basis of human brain development and aging are not fully understood. Changes in methylation are important in development and aging, and plasticity of methylation appears to play a key role in the brain, contributing to processes like the formation of neuronal connections. Previous studies have identified differences in brain methylation patterns among primate species, and the investigators' prior work suggests that genes acting in the nervous system undergo alterations in methylation with advancing age. This project will specifically investigate DNA methylation in four brain regions. The work will build on existing research by taking a comparative approach to identify differences in the trajectories of methylation change in several distinct brain regions across adulthood among four primate species, including humans. Identifying differences among primate brains in age-related change could help us understand the origins of traits distinguishing human brains, including aspects of neurobiological aging.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.