Endocrine Abstracts

Type 2 diabetes mellitus is a life threatening metabolic disease reaching epidemic proportions. Although the molecular basis for this pathology is incompletely understood, genetic and environmental factors, probably in a synergistic manner, contribute to the risk of developing type 2 diabetes. The burden of type 2 diabetes and related co-morbidities on society is enormous, and growing, given that there is no cure in sight. Type 2 diabetes shares many features of “accelerated aging” including insulin resistance, defective oxidative metabolism/mitochondrial function and loss of muscle mass. Strikingly, long-term participation in vigorous exercise programs mitigates secondary aging and reduces disability and mortality. This association advances the notion that exercise promotes “healthy aging”, reduces the impact of metabolic disease, and improves the quality of life. At the molecular level, exercise results in a rapid, but transient change in the epigenome by modifying DNA methylation of the promoters of key genes regulating mitochondrial function and biogenesis in skeletal muscle. Recent evidence suggests that intimate links between epigenetic regulation and the circadian clock exist that are likely to contribute to the plasticity of insulin sensitive organs to exercise and nutrition. Therefore, we are currently addressing whether synchronizing exercise and nutrient interventions to the molecular circadian clock will maximize the health promoting benefits of exercise to enhance insulin sensitivity and mitochondrial biogenesis. This lecture will present new evidence highlighting exercise-responsive treatment targets and optimal exercise intervention strategies to mitigate secondary aging and prevent metabolic disease.