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

Abstract

Edited by: Philip Atherton New Findings r What is the central question of this study?Exercise training by running has an effect on age-related muscle and bone wasting that improves physical activity and quality of life in the elderly. However, the effect of downhill running on age-related muscle and bone wasting, and its mechanisms, are unclear. r What is the main finding and its importance?Gradual downhill running can improve skeletal muscle growth and bone formation by enhancing autophagy and bone morphogenetic protein signalling in aged rats. Therefore, downhill running exercise might be a practical intervention to improve skeletal muscle and bone protection in the elderly.Recent evidence suggests that autophagy and the bone morphogenetic 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-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 −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 and muscle quality similar to gradual uphill training interventions in ageing.

Does Age Have Different Influence between Mountain and City Marathons? - An Analysis from Switzerland

“…For a mountain marathon, the decrease in elasticity could have smaller consequences, due to the fact that in downhill running elasticity of tendons are less important than when running in the flat with the importance of storage of (elastic) energy [40]. The mentioned premise is supported that in collagen tissue alterations of matric proteins and proteoglykans with reduced plasticity and elasticity of ligaments and tendons with increased stiffness result [40][41][42]. Training of these structures could lead to an improvement of age-associated decrease and improve general performance of seniors [36,43].…”

“…Furthermore, associated structures of collagen tissue (tendons and ligaments) are to mention which lose elasticity with increasing age [19,[40][41][42]. For a mountain marathon, the decrease in elasticity could have smaller consequences, due to the fact that in downhill running elasticity of tendons are less important than when running in the flat with the importance of storage of (elastic) energy [40].…”

Schisandra chinensis extract ameliorates age‐related muscle wasting and bone loss in ovariectomized rats

“…It also promoted growth, repair, and remodeling of muscle by the increment of muscle growth factors including p‐AKT, p‐mTOR, MyoD, and myogenin in skeletal muscles of OVX rats. H&E and IHC (p‐mTOR and MyoD) results further confirmed these findings and suggested that C1 treatment protected the structural integrity following gross injuries including polymyositis and strain in OVX rats soleus muscle (Kim et al, ).…”

Interval running training improves age‐related skeletal muscle wasting and bone loss: Experiments with ovariectomized rats

“…Therefore ageing results in slower recovery and functional and structural deficits (McArdle, Vasilaki, & Jackson, ). There are many factors that contribute to osteoporosis and sarcopenia, such as nutritional deficiencies, heredity, oestrogen deficiency, chronic diseases and ageing (Guillemant, Accarie, Peres, & Guillemant, ; Kim, Jeong, Han, & Yi, ; Kim, Lee, & Yi, ). Therefore, prophylactic interventions are needed for the suppression of age‐related skeletal muscle wasting and bone loss after menopause.…”

“…The effect of exercise training is related to the mechanical stimulation on bone caused by contraction of muscle (Oh, Tanaka, Naka, & Igawa, ). Until now, various modes of exercise, such as treadmill running, resistance and swimming training, have been used in many animals to investigate the effect of exercise training (Kim et al., ; Oh et al . ; Sanches, Conti, Sartori, Irigoyen, & De Angelis, ).…”