Multiregion transcriptomic profiling of the primate brain reveals signatures of aging and the social environment

The biology of aging in a social world: insights from free-ranging rhesus macaques

“…Notably, brain structure varied specifically with the number of affiliative social connections, but not other key dimensions of sociality such as social status or position in the social network, as was also the case for certain immune markers (Pavez-Fox et al, 2021). Although an effect of social status could not be detected at a gross neuroanatomical level (Testard et al, 2022), patterns of gene expression in the brain varied with social status and age in a parallel fashion (Chiou, Decasien et al, 2022). Specifically, high-ranking females exhibited younger transcriptomic ages across the brain.…”

“…In the Cayo Santiago study system, cross-sectional sampling of tissues from rhesus macaques removed as part of population management circumvents these limitations. Recent work profiling the transcriptomes of 15 brain regions acquired from healthy adult Cayo Santiago rhesus macaques revealed numerous brain-region specific and multi-region signatures of age (Chiou, Decasien et al, 2022). Many of these multiregion (i.e., "whole-brain") age-associated genes were also identified in humans as markers of a diseased state in Alzheimer's disease.…”

“…Since the macaques in this study did not exhibit any pathologies associated with Alzheimer’s disease, this suggests that some transcriptomic hallmarks of Alzheimer’s disease may manifest earlier in the course of aging, even before neurodegenerative pathologies are present. Further, the accuracy of correctly predicting the sex of these individuals based on non-Y chromosome genes decreases with advancing age– particularly in males (DeCasien, Chiou et al, 2022). This suggests that age-associated breakdowns in tightly regulated suites of genes (transcriptional “decoherence”) may be exacerbated in the brains of males compared to females.…”

“…Although biological sex has historically been ignored in many animal model studies (with a bias towards male-only study designs), the inclusion of both males and females in research is now a priority for many funding agencies (e.g., NIH policy on SABV). Given that the Cayo Santiago population includes approximately equal numbers of males and females, and recent work confirms that rhesus macaques and humans exhibit similar sex differences in the brain transcriptome (Decasien, Chiou et al, 2022), this creates a unique opportunity to consider the potential impacts of biological sex on our variables of interest.…”

Advancing methods for the biodemography of aging within social contexts

“…The observation that breeders receiving help in raising the young age more slowly than the helpers has been observed across several taxa (Berger et al, 2018;Downing et al, 2021), although causality or associations to health remain unknown. In primates, evidence from genome-wide and multi-region transcriptomic studies show that social status affects immune regulation and aging producing evidence of antiviral phenotypes (Snyder-Mackler et al, 2016; and younger relative transcriptional ages (Chiou et al, 2022) in highstatus females. However, associations among social status, health, and aging are often sex-specific and context-dependent.…”