Multiregion transcriptomic profiling of the primate brain reveals signatures of aging and the social environment.
Chiou KL., DeCasien AR., Rees KP., Testard C., Spurrell CH., Gogate AA., Pliner HA., Tremblay S., Mercer A., Whalen CJ., Negrón-Del Valle JE., Janiak MC., Bauman Surratt SE., González O., Compo NR., Stock MK., Ruiz-Lambides AV., Martínez MI., Cayo Biobank Research Unit None., Wilson MA., Melin AD., Antón SC., Walker CS., Sallet J., Newbern JM., Starita LM., Shendure J., Higham JP., Brent LJN., Montague MJ., Platt ML., Snyder-Mackler N.
Aging is accompanied by a host of social and biological changes that correlate with behavior, cognitive health and susceptibility to neurodegenerative disease. To understand trajectories of brain aging in a primate, we generated a multiregion bulk (N = 527 samples) and single-nucleus (N = 24 samples) brain transcriptional dataset encompassing 15 brain regions and both sexes in a unique population of free-ranging, behaviorally phenotyped rhesus macaques. We demonstrate that age-related changes in the level and variance of gene expression occur in genes associated with neural functions and neurological diseases, including Alzheimer's disease. Further, we show that higher social status in females is associated with younger relative transcriptional ages, providing a link between the social environment and aging in the brain. Our findings lend insight into biological mechanisms underlying brain aging in a nonhuman primate model of human behavior, cognition and health.