Effect of Resveratrol on Chemokine Induced Atrophy

Abstract

Changes in the levels of pro-and anti inflammatory cytokines are seen in serum and tissues of older people, reflecting the development of chronic inflammation which is thought to contribute to sarcopenia. Resveratrol has been proposed as a nutritional intervention to modulate inflammation and ameliorate sarcopenia. Our laboratory has identified increases in the pro-inflammatory chemokine IP10 in serum of healthy older people, so this study aimed to determine the effect of IP10 on indices of atrophy in cultured myotubes, and determine whether pre-treatment with resveratrol provided protection against IP10 induced changes. Primary skeletal myoblasts from Sprague dawley rats were isolated, cultured and differentiated into myotubes for 6 days in control media or media containing 1µM of resveratrol. Myotubes were then treated for 24H with IP10 at doses found in serum of elderly (200pg/ml) or young adult humans (150pg/ml) for 24H. At this time, myotube diameter was assessed, cells harvested and qPCR used to analyse atrogin1 mRNA expression. Treatment of myotubes with 200pg/ml IP10 resulted in an increase in atrophin1 mRNA and a decrease in myotube diameter, with the lower dose having no effect. Pre-treatment of myotubes with resveratrol prior to treatment with 200pg/ml IP10 protected against the IP10 induced reduction in myotube diameter and increase in atrogin1. The decrease in myotube diameter and increase in atrogin1 induced only by the level of IP10 found in older people provides evidence that an increased inflammatory environment is a likely contributor to sarcopenia. The ability of physiologically achievable doses of resveratrol to prevent myotube atrophy suggests that resveratrol could act as a therapeutic agent for cytokine induced muscle atrophy and sarcopenia. Funded by BBSRC