Low Circulating Adropin Identifies Vulnerability in Learning-Dependent Cognition in Aged Rhesus Macaques

Identifying reliable biomarkers for age-related cognitive decline (ARCD) is a critical priority, as current diagnostic methods often fall short in predicting individual vulnerability. While conserved biological mechanisms drive aging, direct gerotherapeutic targets for brain aging are lacking. Adropin, a circulating peptide, plays a vital role in regulating metabolic and vascular homeostasis, and has shown associations with cognitive performance in humans. However, its translational relevance and conserved role across species, particularly non-human primates, remained largely unexplored, leaving a gap in understanding its potential as a robust biomarker.

Researchers investigated the association between circulating plasma adropin concentrations and cognitive performance in aged rhesus macaques. The animals were subjected to an increasing food choice test paradigm, designed to assess decision-making, reaction time, and adaptation to novelty or stress. The study focused on how adropin levels correlated with improvements in cognitive tasks, rather than intrinsic baseline performance. This observational approach aimed to identify whether adropin acts as a signal for cognitive resilience or merely executive capacity, using a model highly relevant for human aging studies.

The study revealed a significant association between low plasma adropin concentrations and poor decision-making abilities in aged rhesus macaques. Animals exhibiting higher adropin levels demonstrated faster improvement in reaction time and a notable reduction in the variability of their reaction time. Importantly, intrinsic performance on simple cognitive tasks remained preserved across all animals, suggesting adropin's role is more nuanced than baseline capacity. These beneficial associations were most pronounced under conditions that demanded adaptation to novelty or stress, indicating that adropin may specifically signal cognitive resilience.

The findings parallel mechanistic data from rodent models, linking adropin signaling to improved mitochondrial function, enhanced resistance to oxidative stress, and better hippocampal-dependent learning. This cross-species consistency strengthens the argument for adropin's conserved biological role in cognitive health.