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

Colin Harper,Venkatesh Gopalan,Jorming Goh

doi:10.1186/s12967-021-02737-1

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.

Highlights

Harman’s free radical theory of aging proposed that aging is associated with the accumulation of oxidative damage to proteins, lipids and DNA in living tissues [1]
There will be a discussion on the hallmark mitochondrial changes that occur in skeletal muscle with aging as well as an examination of the evidence for and against aging, or physical inactivity, being the primary cause of abnormal energetics in aged skeletal muscle
Increased Reactive oxygen species (ROS) production is responsible for the increased apoptotic process in type II muscle fibers, leading to preferential loss of such fibers with aging [43]. These results suggest that mitochondrial uncoupling is associated with aging in skeletal muscle and could be an underlying mechanism for inefficient energy production, lowered [adenosine triphosphate (ATP)] within myocytes, and increased apoptosis of type II fibers that manifests as sarcopenia

Summary

Introduction

Harman’s free radical theory of aging proposed that aging is associated with the accumulation of oxidative damage to proteins, lipids and DNA in living tissues [1]. Short and colleagues [14] reported that 16 weeks of ET in men and women aged between 21 and 87 years conferred improvements in peak oxygen uptake (VO2peak), and increases in skeletal muscle mitochondrial enzyme activities and mRNA expressions (citrate synthase and COX) and genes involved in mitochondrial biogenesis (PGC-1α, NRF-1, TFAM). These changes occurred regardless of age, indicating that biological adaptations to exercise training were preserved in aged skeletal muscle. These results make sense in light of the fact that low repetition MVC training as executed in the study, is

Primary outcomes

No change in oxidative capacity or ROS production

Findings

Not applicable