Nobiletin Ameliorates Skeletal Muscle Performance in D‐Galactose‐Induced Aging Mice by Boosting Aerobic Metabolism

The decrease in muscle performance during aging will not only lead to challenges in movement but also increase the risk of fractures, diabetes, and other diseases, which seriously impacts the overall quality of life in the elderly. In the present study, we used D-galactose (D-gal)-induced 8-week C57BL/6J mice to establish a sarcopenia model and to explore the effects of Nobiletin (Nob), a naturally occurring small molecule derived from orange peel, on skeletal muscle function. Our findings demonstrated that Nob significantly improved exercise endurance, grip strength, glucose tolerance, cold tolerance, and energy expenditure in D-gal-induced aging mice. Additionally, Nob ameliorated mitochondrial morphology and enhanced aerobic metabolism of myofibers in D-gal-induced aging mice, thereby providing increased energy for the body. Notably, Nob activated the SIRT1/PGC1α/Nrf2 pathway to enhance superoxide dismutase (SOD) activity and scavenge reactive oxygen species (ROS) in the skeletal muscle of D-gal-induced aging mice. In conclusion, Nob improved the metabolic capacity and function of skeletal muscle by augmenting its antioxidant capacity and optimizing mitochondrial function.