Exercise rescues mitochondrial coupling in aged skeletal muscle: a comparison of different modalities in preventing sarcopenia

Abstract

Skeletal muscle aging is associated with a decline in motor function and loss of muscle mass- a condition known as sarcopenia. The underlying mechanisms that drive this pathology are associated with a failure in energy generation in skeletal muscle, either from age-related decline in mitochondrial function, or from disuse. To an extent, lifelong exercise is efficacious in preserving the energetic properties of skeletal muscle and thus may delay the onset of sarcopenia. This review discusses the cellular and molecular changes in skeletal muscle mitochondria during the aging process and how different exercise modalities work to reverse these changes. A key factor that will be described is the efficiency of mitochondrial coupling-ATP production relative to O₂ uptake in myocytes and how that efficiency is a main driver for age-associated decline in skeletal muscle function. With that, we postulate the most effective exercise modality and protocol for reversing the molecular hallmarks of skeletal muscle aging and staving off sarcopenia. Two other concepts pertinent to mitochondrial efficiency in exercise-trained skeletal muscle will be integrated in this review, including- mitophagy, the removal of dysfunctional mitochondrial via autophagy, as well as the implications of muscle fiber type changes with sarcopenia on mitochondrial function.

Keywords: Aging; Exercise; Mitochondria; Skeletal muscle.

Fig. 1

Concurrent training as a mitoprotective and anti-sarcopenic intervention. Exercise, both in the forms of endurance and resistance training, improves ETC electron flux and mitochondrial oxidative coupling. Specifically, resistance training increases the ratio of complex IV/complex I + III, which in turn minimizes electron leakage and thus ROS generation from complexes I and III, the main cellular sources of superoxide. At the level of mtDNA, this decreases oxidative damage of mtDNA and reduces prevalence of deletion-mutations. In addition, when RT is coupled with endurance training, or with endurance training alone, mtDNA abundance, mitochondrial protein synthesis, and mitochondrial biogenesis all increase. At the level of muscle fibers, these exercise-induced changes prevent age-associated aberrant COX⁻/SDH⁺⁺ phenotypes and preserve type II muscle fibers, altogether functionally staving off sarcopenia. Figure created with BioRender.com