Slow or fast: Implications of myofibre type and associated differences for manifestation of neuromuscular disorders

Abstract

Many neuromuscular disorders can have a differential impact on a specific myofibre type, forming the central premise of this review. The many different skeletal muscles in mammals contain a spectrum of slow‐ to fast‐twitch myofibres with varying levels of protein isoforms that determine their distinctive contractile, metabolic, and other properties. The variations in functional properties across the range of classic ‘slow’ to ‘fast’ myofibres are outlined, combined with exemplars of the predominantly slow‐twitch soleus and fast‐twitch extensor digitorum longus muscles, species comparisons, and techniques used to study these properties. Other intrinsic and extrinsic differences are discussed in the context of slow and fast myofibres. These include inherent susceptibility to damage, myonecrosis, and regeneration, plus extrinsic nerves, extracellular matrix, and vasculature, examined in the context of growth, ageing, metabolic syndrome, and sexual dimorphism. These many differences emphasise the importance of carefully considering the influence of myofibre‐type composition on manifestation of various neuromuscular disorders across the lifespan for both sexes. Equally, understanding the different responses of slow and fast myofibres due to intrinsic and extrinsic factors can provide deep insight into the precise molecular mechanisms that initiate and exacerbate various neuromuscular disorders. This focus on the influence of different myofibre types is of fundamental importance to enhance translation for clinical management and therapies for many skeletal muscle disorders.

Muscle physiology and its relations to the whole body in health and disease

“…This can result in tissuespecific pathologies of muscle diseases. Understanding the complexity of genetics and pharmacology in fast versus slow fibre types shall help to find approaches to fight neuromuscular disorders 8 and disease-related muscle dystrophies. 9 The identification of fibre type compositions of skeletal muscle samples is a crucial part of (patho-)physiological studies.…”

“…Muscle composition and metabolism shifts with species, age, sex, and physical condition. 8,16 A large degree of sexand muscle-related heterogeneity could be detected by implementing the before mentioned deep learning-based image segmentation methods, for fresh and postmortem human skeletal muscle. 10 Therefore, it makes sense that beneficial associations between physical activity and whole-body insulin resistance differ between sexes.…”

Considering the Promise of Vamorolone for Treating Duchenne Muscular Dystrophy

“…This mechanical linkage enables the transmission of force generated by contractile proteins (organised into sarcomeres) within individual myofibres to the whole muscle and tendons, resulting in the movement of different body parts. In the absence of a functional dystrophin protein, the sarcolemma of dystrophic myofibres is vulnerable to mechanical and other damage in response to force generated by the contractile filaments; this damage escalates to myofibre breakdown and necrosis (myonecrosis), which is pronounced in fast contracting myofibres [2]. There is also a much milder form of DMD, with later onset called Becker muscular dystrophy (BMD), that results from different mutations of the DMD gene [1].…”