Impact of Aerobic Exercise Training on Age-Related Changes in Insulin Sensitivity and Muscle Oxidative Capacity

Impact of Aerobic Exercise Training on Age-Related Changes in Insulin Sensitivity and Muscle Oxidative Capacity Kevin R. Short 1 , Janet L. Vittone 2 , Maureen L. Bigelow 1 , David N. Proctor 3 , Robert A. Rizza 1 , Jill M. Coenen-Schimke 1 and K. Sreekumaran Nair 1 1 Department of Internal Medicine, Division of Endocrinology, Mayo Clinic, Rochester, Minnesota 2 Department of General Internal Medicine, Mayo Clinic, Rochester, Minnesota 3 Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota Address correspondence and reprint requests to K. Sreekumaran Nair, PhD, Endocrinology Research Unit, 5–194 Joseph, Mayo Clinic, 200 First St. SW, Rochester, MN 55905. E-mail: nair.sree{at}mayo.edu Abstract Insulin resistance increases and muscle oxidative capacity decreases during aging, but lifestyle changes—especially physical activity—may reverse these trends. Here we report the effect of a 16-week aerobic exercise program ( n = 65) or control activity ( n = 37) performed by men and women aged 21–87 years on insulin sensitivity and muscle mitochondria. Insulin sensitivity, measured by intravenous glucose tolerance test, decreased with age ( r = −0.32) and was related to abdominal fat content ( r = −0.65). Exercise increased peak oxygen uptake ( V o 2peak ; 10%), activity of muscle mitochondrial enzymes (citrate synthase and cytochrome c oxidase, 45–76%) and mRNA levels of mitochondrial genes (COX4, ND4, both 66%) and genes involved in mitochondrial biogenesis (PGC-1α, 55%; NRF-1, 15%; TFAM, 85%). Exercise also increased muscle GLUT4 mRNA and protein (30–52%) and reduced abdominal fat (5%) and plasma triglycerides (25%). None of these changes were affected by age. In contrast, insulin sensitivity improved in younger people but not in middle-aged or older groups. Thus, the muscle mitochondrial response to 4 months of aerobic exercise training was similar in all age-groups, although the older people did not have an improvement in insulin sensitivity. GCRC, General Clinical Research Center NRF, nuclear respiratory factor PGC-1α, PPAR-γ coactivator 1α PPAR, peroxisome proliferator–activated receptor TFAM, mitochondrial transcription factor A Vo2peak, peak oxygen uptake SI, insulin sensitivity Footnotes Accepted May 1, 2003. Received October 31, 2002. Revision received May 1, 2003. DIABETES