Gradual downhill running improves age-related skeletal muscle and bone weakness: Implication of autophagy and bone morphogenetic proteins

Recent evidence suggests that autophagy and bone morphogenetic protein signaling pathway regulate skeletal muscle growth and bone formation in aged rats. However, the effect of downhill running on muscle growth and bone formation is not well understood. Thus, we investigated the effect of downhill and uphill running on age-related muscle and bone weakness. Young and late middle-aged rats were randomly assigned to control groups; young (YC) and late middle-aged (LMC), and two types of running training groups: late middle-aged downhill (LMD) and late middle-aged uphill (LMU). Training was progressively carried out on a treadmill at a speed of 21 m/min with a slope of +10° for uphill training vs 16 m/min with a slope of –16° for downhill training: 60 min/day, 5 days/week for 8 weeks respectively. Downhill and uphill training increased the autophagy-related proteins 5 (ATG5), microtubule-associated protein light chain (LC3-Ⅱ), Beclin-1, and p62 proteins in aged rats. In addition, superoxide dismutase (SODs), heme oxygenase-1 (HO-1), and bone morphogenetic proteins (BMPs) signaling pathway were also elevated. Phosphorylation of mammalian target of rapamycin (p-mTOR) and myogenic differentiation (MyoD) were increased significantly in LMD and LMU groups. Consequently in the femur, BMP–2, –7 and autophagy molecules were expressed highly in LMD and LMU groups. These results suggest that both of the downhill and uphill training appeared to positively affect autophagy molecules and BMPs expression, respectively. Particularly, these physiological adaptations from gradual downhill training have an effect on bone morphological changes and muscle quality similar to gradual uphill training interventions in aging.

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