Autophagy Mediates the Metabolic Benefits of Endurance Training

Abstract

### Exercise-Induced BCL2-Regulated Autophagy Is Required for Muscle Glucose Homeostasis He et al Nature . 2012;481:511–515. In a recent issue of Nature, He et al demonstrate that autophagy is required for optimal physical endurance as well as for the beneficial effects of exercise on glucose and lipid metabolism. These data not only shed new insights into the mechanisms whereby exercise is healthy, but also indirectly strengthen the notion that autophagy exerts lifespan-extending effects. Macroautophagy (hereafter referred to as autophagy) is a finely regulated catabolic pathway for the degradation of intracellular constituents including portions of the cytoplasm, organelles, and protein aggregates. In virtually all cells, baseline levels of autophagy ensure the removal of potentially dangerous structures such as permeabilized mitochondria, thus contributing to the maintenance of intracellular homeostasis.1 Moreover, several (though probably not all) cell types upregulate autophagy in response to a wide array of adverse conditions, encompassing nutrient shortage, hypoxia, xenobiotics, and invasion by intracellular pathogens.2 Thus, in the majority of settings, autophagy constitutes a cytoprotective response by which cells preserve or attempt to reestablish homeostasis. However, autophagy can also contribute to the execution of cell death, in particular in developmental scenarios or during the response of some types of cancer cells to specific chemotherapeutics.3 Defects in the autophagic machinery have been associated with multiple distinct human diseases, including neurodegenerative disorders, altered responses to infection, cardiovascular conditions, and cancer.4 In addition, autophagy has been suggested to be a key regulator of healthy aging, for at least 3 reasons. First, genetic or pharmacological inhibition of autophagy triggers degenerative changes that resemble those associated with aging. Second, both normal and pathological aging are linked to a reduced autophagic potential. Third, inhibition of autophagy compromises the longevity-promoting effects of several distinct maneuvers that extend lifespan in model organisms, including inhibition of the insulin-like growth factor …