Exercise training, but not resveratrol, improves metabolic and inflammatory status in skeletal muscle of aged men

Key points Ageing is associated with lifestyle-related metabolic diseases, and exercise training has been suggested to counteract such metabolic deteriorations. The natural antioxidant resveratrol has been reported to exert 'exercise-like' health beneficial metabolic and anti-inflammatory effects in rodents, but little is known about the metabolic effects of resveratrol supplementation alone and in combination with exercise training in humans. The present findings showed that exercise training markedly improved muscle endurance, increased content and activity of oxidative proteins in skeletal muscle and reduced markers of oxidative stress and inflammation in skeletal muscle of aged men. Resveratrol alone did not elicit metabolic effects in healthy aged subjects, but even impaired the exercise training-induced improvements in markers of oxidative stress and inflammation in skeletal muscle. The aim was to investigate the metabolic and anti-inflammatory effects of resveratrol alone and when combined with exercise training in skeletal muscle of aged human subjects. Healthy, physically inactive men (60-72years old) were randomized to either 8weeks of daily intake of 250mg resveratrol or placebo or to 8weeks of high-intensity exercise training with 250mg resveratrol or placebo. Before and after the interventions, resting blood samples and muscle biopsies were obtained and a one-legged knee-extensor endurance exercise test was performed. Exercise training increased skeletal muscle peroxisome proliferator-activated receptor-gamma co-activator-1 alpha mRNA similar to 1.5-fold, cytochromec protein similar to 1.3-fold, cytochromec oxidaseI protein similar to 1.5-fold, citrate synthase activity similar to 1.3-fold, 3-hydroxyacyl-CoA dehydrogenase activity similar to 1.3-fold, inhibitor of kappa B-alpha and inhibitor of kappa B-beta protein content similar to 1.3-fold and time to exhaustion in the one-legged knee-extensor endurance exercise test by similar to 1.2-fold, with no significant additive or adverse effects of resveratrol on these parameters. Despite an overall similar to 25% reduction in total acetylation level in skeletal muscle with resveratrol, no exclusive resveratrol-mediated metabolic effects were observed on the investigated parameters. Notably, however, resveratrol blunted an exercise training-induced decrease (similar to 20%) in protein carbonylation and decrease (similar to 40%) in tumour necrosis factor alpha mRNA content in skeletal muscle. In conclusion, resveratrol did not elicit metabolic improvements in healthy aged subjects; in fact, resveratrol even impaired the observed exercise training-induced improvements in markers of oxidative stress and inflammation in skeletal muscle. Collectively, this highlights the metabolic efficacy of exercise training in aged subjects and does not support the contention that resveratrol is a potential exercise mimetic in healthy aged subjects.