Exploring for compounds that enhance motor function using muscle fatigue-model mice

Abstract

Musculoskeletal disease can be a serious condition associated with aging that may lead to fractures and a bedridden state due to decreased motor function. In addition to exercise training to increase muscle mass, increasing muscle function with the intake of functional foods is an effective treatment strategy for musculoskeletal disease. The redox imbalance caused by increased reactive oxygen species (ROS) induce muscle hypofunction. Mammals have various antioxidants systems that protect tissue and cells from ROS. Superoxide dismutase (SOD) is an antioxidant enzyme that converts superoxide to hydrogen peroxide, which is further detoxified to water and O2 by catalase and GPx enzymes. SOD2 is constitutively and ubiquitously expressed in the mitochondria to regulate the redox balance in the cells of tissues. The loss of SOD2 induces mitochondrial redox imbalance by increasing the generation of superoxide, resulting in mitochondrial dysfunction in cells and several tissues, indicating important role of SOD2 for living body. Previously, we demonstrated that, musclespecific SOD2-deficient mice (muscle-Sod2^-/-) show a severe disturbance in exercise in association with increased mitochondrial reactive oxygen species, as well as mitochondrial dysfunction and muscle damage. Muscle-Sod2^-/- mice are expected to be used as a muscle fatigue model for research applications for elucidating the mechanism of muscle dysfunction and improving motor function. In this review, we describe the pathology of skeletal muscle in muscle-Sod2^-/- mice and introduce the search for functional foods that enhance motor function using these deficient mice.