Transcriptomic signatures of the aging brain at single-cell resolution

Aging is a major risk factor for neurodegenerative diseases that impose tremendous burdens on people and societies today. To understand trajectories of neurological aging in a primate, we generated one of the most comprehensive brain transcriptional datasets to date in a unique population of naturalistic, behaviorally phenotyped rhesus macaques. In this experiment, we generated 71,863 single-nucleus RNA-seq transcriptomes from the dorsolateral prefrontal cortex of 24 adult females spanning all ages. We find that, of all tested cell classes, oligodendrocytes were the only cell type to significantly increase in proportion with age. We also identify hundreds of genes that change significantly with age in one or more cell types, providing a valuable window into cell-type-specific aging in the prefrontal cortex. Our findings lend insight into biological mechanisms underlying brain aging and indicate promising directions for improving neurological health. Overall design: 71,863 single-nucleus transcriptomes derived from the dorsolateral prefrontal cortex of 24 female rhesus macaques spanning the natural age distribution.