Study Title:

Contribution of the mitochondria to Locomotor Muscle Dysfunction in COPD patients.

Study Abstract

COPD is a significant public health challenge, notably set to become the third leading cause of death and fifth leading cause of chronic disability worldwide by the next decade. Skeletal muscle impairment is now recognized as a disabling, extra-pulmonary consequence of COPD and associated with reduced quality of life and premature mortality. Because COPD typically manifests in older individuals, these clinical features may overlie normal age-associated declines in muscle function and performance. While physical inactivity, oxidative stress, inflammation, hypoxia, malnutrition and medications all likely contribute to this co-morbidity, a better understanding of the underlying mechanism is needed to develop effective therapies. Mitochondrial alterations including reductions in density and oxidative enzyme activity, increased mitochondrial reactive oxygen species production and induction of muscle proteolysis including autophagy have been described. This review focuses on the perspective that mitochondrial alterations contribute to impaired locomotor muscle performance in COPD patients by reducing oxidative capacity and thus endurance, as well as by triggering proteolysis and thus contributing to atrophy and weakness. We discuss how the potential underlying mechanisms converge on mitochondria by targeting the PGC-1α signalling pathway thereby reducing mitochondrial biogenesis and muscle oxidative capacity and potentially increasing fiber atrophy, and how taking advantage of normal muscle plasticity and mitochondrial biogenesis may reverse this pathophysiology. We propose recent therapeutic strategies aimed at increasing PGC-1α levels, such as endurance training and exercise mimetics with the strong rationale for increasing mitochondrial biogenesis and function and thus improving the muscle phenotype in COPD.
Copyright © 2015 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Study Information

Contribution of the mitochondria to Locomotor Muscle Dysfunction in COPD patients.
2015 December

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