Label-free Quantitative Protein Profiling of vastus lateralis Muscle During Human Aging

Théron, Laëtitia; Gueugneau, Marine; Coudy, Cécile; Viala, Didier; Bijlsma, Astrid Y.; Butler-Browne, Gillian; Maier, Andrea B.; Béchet, Daniel; Chambon, Christophe

doi:10.1074/mcp.m113.032698

Cited by 51 publications

(48 citation statements)

References 56 publications

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“…However, although these analyses are important for discovery of novel pathways with aging, it should be acknowledged that changes at the mRNA level are not always reflected at the level of proteins, and a greater divergence of results has been observed when proteomic approaches have been employed (Table 2). Theron et al (159) identified 35 proteins that were differentially expressed during aging, most of which were downregulated and involved in energy metabolism, the myofilament, or the cytoskeleton. In reviewing the literature, Baraibar et al (8) concluded that most proteomic studies reported decrements in key mitochondrial enzymes in aging muscle, although some investigators have indicated increased levels (Refs.…”

Section: Transcriptomic and Proteomic Mitochondrial Characteristics Omentioning

confidence: 99%

Mitochondria, Muscle Health, and Exercise with Advancing Age

2015

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Skeletal muscle health is dependent on the optimal function of its mitochondria. With advancing age, decrements in numerous mitochondrial variables are evident in muscle. Part of this decline is due to reduced physical activity, whereas the remainder appears to be attributed to age-related alterations in mitochondrial synthesis and degradation. Exercise is an important strategy to stimulate mitochondrial adaptations in older individuals to foster improvements in muscle function and quality of life.Heather N. Carter, Chris C. W. The process of aging exploits the malleable nature of skeletal muscle. The age-related loss of muscle mass was termed sarcopenia, based on the Greek (sarx, flesh) and (penia, poverty) in 1988 (139). Accompanying this loss are profound architectural and molecular changes that alter muscle quality and are manifested in functional limitations. Decreases in muscle fiber number as well as fiber cross-sectional area are both contributing factors to sarcopenia (92) and consequently adversely affect force production (strength) (46, 63) and endurance of the older individual (12). Muscle mass typically peaks in the mid-20s (12, 34,92), and thereafter several distinct phases of muscle loss have been identified. In the third to fifth decade of life, a slow rate of muscle mass loss is noted, amounting to ϳ10% in total (34,92). In later adulthood (Ͼ45 yr), the rate of muscle loss increases, with appraisals ranging between 0.5 and 1.4% per year (12, 34,69). Even more dramatic changes are noted beyond the sixth decade of life. Along with the functional impairments imposed by sarcopenia, are the associated escalations in health care costs, along with coincident rises in metabolic diseases (e.g., Type 2 diabetes, obesity) and a greater risk of falls (67). In the U.S., it is expected that those 65 years of age and over will comprise ϳ20% of the population, or ϳ72 million people, by the year 2030 (20). Since the proportion of older adults is increasing, continued research into the mechanisms of muscle loss is warranted, along with the investigation of therapeutic strategies that can mitigate muscle atrophy during aging. Mitochondria have been implicated as potential mediators of sarcopenia. Recently, it has been suggested that dysfunction of these organelles can be considered a feature of aging (105). However, considerable controversy exists regarding the extent to which muscle mitochondria may be dysfunctional with aging, and thereby contribute to the loss of this tissue. Thus the purpose of this review is to examine the literature with respect to mitochondrial content and function in muscle with advancing age, and provide a perspective on the effectiveness of endurance/aerobic exercise as an intervention for mitochondrial biogenesis and muscle homeostasis in older individuals. Structural Features of Muscle Relevant to SarcopeniaIn young, healthy individuals, skeletal muscle comprises ϳ40% of total body mass and is important for locomotion and whole body metabolism. Myosin ATPase histochemistry and electrop...

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Section: Transcriptomic and Proteomic Mitochondrial Characteristics Omentioning

confidence: 99%

Mitochondria, Muscle Health, and Exercise with Advancing Age

2015

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“…The predominant method has been 2-dimensional gel electrophoresis (2DGE) followed by in-gel trypsin digestion and tandem MS (MS/MS) (14–16). More recently, 1-dimensional gel electrophoresis (1DGE) has been utilized in the characterization of normal, aging, and dystrophic skeletal muscle (17–19). Although differentially expressed proteins in muscular dystrophy samples were identified using the 2DGE proteomic strategy, a number of technical shortcomings make the use of this approach impractical for the study of integral membrane proteins by MS/MS.…”

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confidence: 99%

Molecular Signatures of Membrane Protein Complexes Underlying Muscular Dystrophy

Turk

Hsiao

Smits

et al. 2016

Molecular & Cellular Proteomics

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Mutations in genes encoding components of the sarcolemmal dystrophin-glycoprotein complex (DGC) are responsible for a large number of muscular dystrophies. As such, molecular dissection of the DGC is expected to both reveal pathological mechanisms, and provides a biological framework for validating new DGC components. Establishment of the molecular composition of plasma-membrane protein complexes has been hampered by a lack of suitable biochemical approaches. Here we present an analytical workflow based upon the principles of protein correlation profiling that has enabled us to model the molecular composition of the DGC in mouse skeletal muscle. We also report our analysis of protein complexes in mice harboring mutations in DGC components. Bioinformatic analyses suggested that cell-adhesion pathways were under the transcriptional control of NFκB in DGC mutant mice, which is a finding that is supported by previous studies that showed NFκB-regulated pathways underlie the pathophysiology of DGC-related muscular dystrophies. Moreover, the bioinformatic analyses suggested that inflammatory and compensatory mechanisms were activated in skeletal muscle of DGC mutant mice. Additionally, this proteomic study provides a molecular framework to refine our understanding of the DGC, identification of protein biomarkers of neuromuscular disease, and pharmacological interrogation of the DGC in adult skeletal muscle https://www.mda.org/disease/congenital-muscular-dystrophy/research.

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“…The pathophysiological mechanisms of sarcopenia are believed to be highly complex resulting in a multi-factorial etiology. Recent proteomic studies have established extensive changes in the skeletal muscle proteome during the natural aging process [210,211,212], whereby gel-based proteomics has been instrumental in the initial cataloguing of the aged muscle proteome [213,214,215]. Skeletal muscle aging is closely associated with persistent impairments of the peripheral nervous system, which trigger excitation-contraction uncoupling and pathophysiological cycles of denervation and faulty reinnervation.…”

Section: Comparative Skeletal Muscle Proteomics Using Two-dimensiomentioning

confidence: 99%

Comparative Skeletal Muscle Proteomics Using Two-Dimensional Gel Electrophoresis

Murphy¹,

Dowling²,

Ohlendieck³

2016

Proteomes

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The pioneering work by Patrick H. O’Farrell established two-dimensional gel electrophoresis as one of the most important high-resolution protein separation techniques of modern biochemistry (Journal of Biological Chemistry 1975, 250, 4007–4021). The application of two-dimensional gel electrophoresis has played a key role in the systematic identification and detailed characterization of the protein constituents of skeletal muscles. Protein changes during myogenesis, muscle maturation, fibre type specification, physiological muscle adaptations and natural muscle aging were studied in depth by the original O’Farrell method or slightly modified gel electrophoretic techniques. Over the last 40 years, the combined usage of isoelectric focusing in the first dimension and sodium dodecyl sulfate polyacrylamide slab gel electrophoresis in the second dimension has been successfully employed in several hundred published studies on gel-based skeletal muscle biochemistry. This review focuses on normal and physiologically challenged skeletal muscle tissues and outlines key findings from mass spectrometry-based muscle proteomics, which was instrumental in the identification of several thousand individual protein isoforms following gel electrophoretic separation. These muscle-associated protein species belong to the diverse group of regulatory and contractile proteins of the acto-myosin apparatus that forms the sarcomere, cytoskeletal proteins, metabolic enzymes and transporters, signaling proteins, ion-handling proteins, molecular chaperones and extracellular matrix proteins.

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Label-free Quantitative Protein Profiling of vastus lateralis Muscle During Human Aging

Cited by 51 publications

References 56 publications

Mitochondria, Muscle Health, and Exercise with Advancing Age

Mitochondria, Muscle Health, and Exercise with Advancing Age

Molecular Signatures of Membrane Protein Complexes Underlying Muscular Dystrophy

Comparative Skeletal Muscle Proteomics Using Two-Dimensional Gel Electrophoresis

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