Background/aim: Age-related metabolic diseases are often associated with low-grade inflammation. The aim of the present study was to investigate the role of the transcriptional co-activator PGC-1 alpha in the potential beneficial effects of exercise training and/or resveratrol in the prevention of age-associated low-grade inflammation. To address this, a long-term voluntary exercise training and resveratrol supplementation study was conducted. Experimental setup: Three month old whole body PGC-1 alpha KO and WT mice were randomly assigned to four groups: untrained chow-fed, untrained chow-fed supplemented with resveratrol, chow-fed voluntarily exercise trained and chow-fed supplemented with resveratrol and voluntarily exercise trained. The intervention lasted 12 months and three month old untrained chow-fed mice served as young controls. Results: Voluntary exercise training prevented an age-associated increase (p < 0.05) in systemic IL-6 and adiposity in WT mice. PGC-1 alpha expression was required for a training-induced prevention of an age-associated increase (p < 0.05) in skeletal muscle TNF alpha protein. Independently of PGC-1 alpha, both exercise training and resveratrol prevented an age-associated increase (p < 0.05) in skeletal muscle protein carbonylation. Conclusion: The present findings highlight that exercise training is a more effective intervention than resveratrol supplementation in reducing age-associated inflammation and that PGC-1 alpha in part is required for the exercise training-induced anti-inflammatory effects. (C) 2013 Elsevier Inc. All rights reserved.