The 88th Annual Meeting of the American Association of Physical Anthropologists (2019)


Transcriptional signatures of the aging nonhuman primate brain

KENNETH L. CHIOU1,2, ALEX R. DECASIEN3,4, MICHAEL J. MONTAGUE5, CHET C. SHERWOOD6, MICHAEL L. PLATT5,7,8, JAMES P. HIGHAM3,4 and NOAH SNYDER-MACKLER1,2,9.

1Department of Psychology, University of Washington, 2Nathan Shock Center of Excellence in the Basic Biology of Aging, University of Washington, 3Department of Anthropology, New York University, 4New York Consortium in Evolutionary Primatology, 5Department of Neuroscience, University of Pennsylvania, 6Department of Anthropology, The George Washington University, 7Department of Psychology, University of Pennsylvania, 8Department of Marketing, University of Pennsylvania, 9Center for Studies in Demography & Ecology, University of Washington

March 29, 2019 11:30, CC Ballroom A Add to calendar

The primate brain is capable of rapidly and reliably processing complex stimuli. These abilities decline with age, which in humans sometimes manifests in neurodegenerative diseases such as Alzheimer's. Yet little is understood about heterogeneity of the aging process across brain regions and cells. To address this gap, we characterized gene expression in brains from a cross-sectional sample of a model population: the rhesus macaques of Cayo Santiago. We sequenced transcriptomes from 160 samples across 8 brain regions involved in various cognitive and sensorimotor functions. As expected, transcriptomes were highly region-specific, with age strongly influencing the transcriptional landscape of all tested regions. Interestingly, the number and identity of age-associated genes differed across regions. The superior temporal sulcus was most strongly affected, with 1,132 genes altered by age. Apart from differences in the number of age-associated genes, regions also varied in the direction and magnitude of changes in gene expression. Further, the magnitude of age-associated effects were distributed unevenly across regions, suggesting that the molecular consequences of aging are largely region-specific. We are now sequencing single-cell transcriptomes to better understand cell-type heterogeneity in aging. We are also testing the impact of social and environmental factors on age-related transcriptional changes. Together, our work underscores the importance of primate models for understanding the intersections of environment and evolution with regard to the aging phenotype.

This work is supported by the National Institutes of Health (NIA R00-AG051764, NIMH R01-MH108627, NIA T32-AG000057) and the National Science Foundation (BCS 1752393).