Fiber-Type Shifting in Sarcopenia of Old Age: Proteomic Profiling of the Contractile Apparatus of Skeletal Muscles

Abstract

The progressive loss of skeletal muscle mass and concomitant reduction in contractile strength plays a central role in frailty syndrome. Age-related neuronal impairments are closely associated with sarcopenia in the elderly, which is characterized by severe muscular atrophy that can considerably lessen the overall quality of life at old age. Mass-spectrometry-based proteomic surveys of senescent human skeletal muscles, as well as animal models of sarcopenia, have decisively improved our understanding of the molecular and cellular consequences of muscular atrophy and associated fiber-type shifting during aging. This review outlines the mass spectrometric identification of proteome-wide changes in atrophying skeletal muscles, with a focus on contractile proteins as potential markers of changes in fiber-type distribution patterns. The observed trend of fast-to-slow transitions in individual human skeletal muscles during the aging process is most likely linked to a preferential susceptibility of fast-twitching muscle fibers to muscular atrophy. Studies with senescent animal models, including mostly aged rodent skeletal muscles, have confirmed fiber-type shifting. The proteomic analysis of fast versus slow isoforms of key contractile proteins, such as myosin heavy chains, myosin light chains, actins, troponins and tropomyosins, suggests them as suitable bioanalytical tools of fiber-type transitions during aging.

Mass Spectrometry-Based Proteomic Technology and Its Application to Study Skeletal Muscle Cell Biology

“…Excellent markers of the various subtypes of myofibers are represented by slow myosin heavy chain MyHC-1(beta) and the fast myosin heavy chains MyHC-2a, MyHC-2x and MyHC-2b [274]. The biochemical profiling of the contractile apparatus of skeletal muscles has recently been reviewed and this article lists the most abundant fiber type-specific markers, i.e., isoforms of myosin heavy chains, myosin light chains, troponins and tropomyosins, that were confirmed by proteomics [47]. The identification of individual fiber types using contractile apparatus proteins can be conveniently combined with reliable markers that belong to the Ca 2+ -handling complexes of skeletal muscles.…”

“…Thus, a detailed understanding of normal muscle function and its cellular regulation including the dynamics of the skeletal muscle proteome, as compared to muscle wasting, is important for diverse biological and biomedical disciplines. This includes crucial aspects of lifestyle biology, health science and clinical medicine, including sports and exercise physiology [39,40], electro-stimulation therapy, research into skeletal muscle plasticity [43,257], disuse-related muscular atrophy and the effects of re-innervation [41,258,259], space flight medicine [260,261], neuromuscular diseases [44,45], frailty-associated muscle aging and biogerontology [47,[262][263][264], forensic medicine [265,266] and the meat industry [267,268]. Important topics in muscle cell biology that are gaining steady interest are the regulation of skeletal muscle mass [269], myokine signaling [270] and muscle-bone-fat crosstalk [271].…”

“…These articles give a comprehensive overview of the many applications of MS-based analyses to improve our molecular and cellular understanding of skeletal muscle protein diversity, modifications and dynamics. Previous reviews have extensively covered the proteomic analysis of human skeletal muscle [20,37], the impact of exercise [38][39][40], disuse-related muscular atrophy [41], skeletal muscle plasticity [42,43], neuromuscular diseases [44,45] and frailty-associated muscle aging [46,47]. Building on these articles, we provide here a general synopsis of skeletal muscle proteomics and its scientific importance for the field of basic and applied myology.…”

A novel deep proteomic approach in human skeletal muscle unveils distinct molecular signatures affected by aging and resistance training

“…While other -omics-based approaches exist (i.e., genomics, epigenomics, transcriptomics, and metabolomics), it has been posited that proteomic signatures likely best translate to cellular and tissue phenotypes (17). Past proteomic investigations have provided tremendous insight as to how myofiber type, aging, and exercise training affect the skeletal muscle molecular milieu (1,14,(18)(19)(20)(21)(22). Notwithstanding, skeletal muscle-based proteomics poses technical challenges.…”

Muscle Atrophy: From Bench to Bedside

“…This work paves the way for deeper investigation on the TGF-β/BMP balance, which may lead to the development of new strategies to fight against muscle atrophy. Dowling et al [6] addressed the potential use of markers for addressing the progressive loss of muscle mass and strength in elderlies, i.e., sarcopenia. The authors compiled proteomic data from elderlies and aged rodents and observed that the fiber shift (from fast to slow) appearing during aging may be a good readout for witnessing the appearance of sarcopenia.…”