Environmental Enrichment Improves Motor Function and Muscle Transcriptome of Aged Mice

Abstract Aging results in the progressive decline of muscle strength. Interventions to maintain muscle strength may mitigate the age‐related loss of physical function, thus maximizing health span. The work on environmental enrichment (EE), an experimental paradigm recapitulating aspects of an active lifestyle, has revealed EE‐induced metabolic benefits mediated by a brain‐fat axis across the lifespan of mice. EE initiated at 18‐month of age shows a trend toward an increased mean lifespan. While previous work described EE's influences on the aging dynamics of several central‐peripheral processes, its influence on muscle remained understudied. Here, the impact of EE is investigated on motor function, neuromuscular physiology, and the skeletal muscle transcriptome. EE is initiated in 20‐month‐old mice for a five‐month period. EE mice exhibit greater relative lean mass that is associated with improved mobility and hindlimb grip strength. Transcriptomic profiling of muscle tissue reveals an EE‐associated enrichment of gene expression within several metabolic pathways related to oxidative phosphorylation and the TCA cycle. Many mitochondrial‐related genes—several of which participate in the electron transport chain—are upregulated. Stress‐responsive signaling pathways are downregulated because of EE. The results suggest that EE improves motor function—possibly through preservation of mitochondrial function—even late in life.