The molecular athlete: exercise physiology from mechanisms to medals

Abstract

Human skeletal muscle demonstrates remarkable plasticity, adapting to numerous external stimuli including the habitual level of contractile loading. Accordingly, muscle function and exercise capacity encompass a broad spectrum, from inactive individuals with low levels of endurance and strength, to elite athletes who produce prodigious performances underpinned by pleiotropic training-induced muscular adaptations. Our current understanding of the signal integration, interpretation and output coordination of the cellular and molecular mechanisms that govern muscle plasticity across this continuum is incomplete. As such, training methods and their application to elite athletes largely rely on a "trial and error" approach with the experience and practices of successful coaches and athletes often providing the bases for "post hoc" scientific enquiry and research. This review provides a synopsis of the morphological and functional changes along with the molecular mechanisms underlying exercise adaptation to endurance- and resistance-based training. These traits are placed in the context of innate genetic and inter-individual differences in exercise capacity and performance, with special considerations given to the ageing athletes. Collectively, we provide a comprehensive overview of skeletal muscle plasticity in response to different modes of exercise, and how such adaptations translate from "molecules to medals".

Molecular control of endurance training adaptation in mouse skeletal muscle

“…However, the main task of skeletal muscle is the generation of force for different types of contractile activities, including strength, endurance, fine motor control, posture or breathing. Skeletal muscle thus not only exhibits broad morphological and functional specification, but also a remarkable adaptive plasticity to react to internal and external perturbations 4 . Remodeling of skeletal muscle requires interventions that disrupt homeostasis, to which muscle will progressively adapt only if repeated over time 3,4 .…”

“…Skeletal muscle thus not only exhibits broad morphological and functional specification, but also a remarkable adaptive plasticity to react to internal and external perturbations 4 . Remodeling of skeletal muscle requires interventions that disrupt homeostasis, to which muscle will progressively adapt only if repeated over time 3,4 . Morphologically, such adaptations are well described, e.g.…”

“…In light of the powerful health benefits conferred by either modality of exercise 6,7 , it however is surprising that the molecular underpinnings of muscle plasticity in exercise are still only rudimentarily understood 4 . In particular, the mechanistic framework that links the perturbations evoked by individual, acute exercise bouts to long-term training adaptations are largely unknown 3,4 . Additionally, it is unclear how the training status affects the molecular response to an acute bout of exercise, and how changes in gene expression are ultimately linked to persistent modulation of protein levels, organelle function and tissue plasticity.…”

“…Accordingly, the expression of many genes is not following an attenuating pattern, instead showing an exacerbated response in trained muscle, as described for the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) 20 . Of note, PGC-1α and most other postulated key regulatory factors in exercise adaptation in skeletal muscle, including the AMP-dependent protein kinase (AMPK), the mammalian target of rapamycin (mTOR), or the calcium-dependent proteins calcineurin A (CnA) and calcium/calmodulin-dependent kinase (CaMK) are only very transiently modulated 4 . Therefore, little knowledge about the chronic, persistent mechanistic network in training adaptation exists.…”

“…Skeletal muscle exerts pleiotropic functions, from thermoregulation through shivering, to endocrine signaling by myokines and myometabolites, and detoxification of endogenous compounds, e.g. kynurenines or aberrantly high levels of ketone bodies [1][2][3][4][5] . However, the main task of skeletal muscle is the generation of force for different types of contractile activities, including strength, endurance, fine motor control, posture or breathing.…”