Effect of lifelong resveratrol supplementation and exercise training on skeletal muscle oxidative capacity in aging mice; impact of PGC-1α

Background: The present study tested the hypothesis that lifelong resveratrol (RSV) supplementation counteracts an age-associated decrease in skeletal muscle oxidative capacity through peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1 alpha and that RSV combined with lifelong exercise training (EX) exerts additive effects through PGC-1 alpha in mice. Methods: 3 month old PGC-1 alpha whole body knockout (KO) and wild type (WT) littermate mice were placed in cages with or without running wheel and fed either standard chow or standard chow with RSV supplementation (4 g/kg food) for 12 months. Young (3 months of age), sedentary mice on standard chow served as young controls. A graded running performance test and a glucose tolerance test were performed 2 and 1 week, respectively, before euthanization where quadriceps and extensor digitorum longus (EDL) muscles were removed. Results: In PGC-1 alpha KO mice, quadriceps citrate synthase (CS) activity, mitochondrial (mt) DNA content as well as pyruvate dehydrogenase (PDH)-E1 alpha, cytochrome (Cyt) c and vascular endothelial growth factor (VEGF) protein content were 20-75% lower and, EDL capillary-to-fiber (C:F) ratio was similar to 15-30% lower than in WT mice. RSV and/or EX had no effect on the C: F ratio in EDL. CS activity (P = 0.063) and mtDNA content (P = 0.013) decreased with age in WT mice, and CS activity, mtDNA content, PDH-E1 alpha protein and VEGF protein increased similar to 1.5-1.8-fold with lifelong EX in WT, but not in PGC-1 alpha KO mice, while RSV alone had no significant effect on these proteins. Conclusion: Lifelong EX increased activity/content of oxidative proteins, mtDNA and angiogenic proteins in skeletal muscle through PGC-1 alpha, while RSV supplementation alone had no effect. Combining lifelong EX and RSV supplementation had no additional effect on skeletal muscle oxidative and angiogenic proteins. (C) 2013 Elsevier Inc. All rights reserved.