Low circulating adropin concentrations identify vulnerability in learning-dependent cognitive performance in aged rhesus macaques.

Abstract

Identifying biomarkers that identify vulnerability to age-related cognitive decline is a major priority in aging research. Adropin, a circulating peptide that regulates metabolic and vascular homeostasis, has been associated with cognitive performance in humans, but its relevance across species has remained unclear. Here we report low plasma adropin concentrations associate with poor decision-making in aged rhesus macaques subject to an increasing food choice test paradigm. Animals with higher adropin levels exhibited faster improvement in reaction time and reductions of variability in reaction time, whereas intrinsic performance on simple tasks was preserved. These associations were most apparent under conditions requiring adaptation to novelty or stress, suggesting that adropin may signal cognitive resilience rather than baseline executive capacity. The findings parallel mechanistic data from rodent models linking adropin signaling to mitochondrial function, resistance to oxidative stress, and hippocampal-dependent learning. Together, these results support measurements of circulating adropin as a conserved, translational biomarker of cognitive aging and a potential therapeutic target.