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

Recent evidence suggests that autophagy and the bonemorphogenetic protein (BMP) signalling 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-relatedmuscle 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 (latemiddle-aged downhill, LMD; and late middle-aged uphill, LMU). Training was progressively carried out on a treadmill at a speed of 21 m min(-1) with a slope of +10 deg for uphill training versus 16 m min(-1) with a slope of -16 deg for downhill training, both for 60 min day(-1), 5 days week(-1) for 8 weeks. Downhill and uphill training increased autophagy-related protein 5, microtubule-associated protein light chain, Beclin-1 and p62 proteins in aged rats. In addition, superoxide dismutase, haem oxygenase-1 and the BMP signalling pathway were elevated. Phosphorylation of mammalian target of rapamycin and myogenic differentiation were increased significantly in the LMD and LMU groups. Consequently, in the femur, BMP-2, BMP-7 and autophagy molecules were highly expressed in the LMD and LMU groups. These results suggest that both downhill and uphill training appear to have a positive effect on expression of autophagy molecules and BMPs. In particular, these physiological adaptations from gradual downhill exercise have an effect on bone morphological changes andmuscle quality similar to gradual uphill training interventions in ageing.