The molecular basis of skeletal muscle atrophy

Abstract

. The molecular basis of skeletal muscle atrophy. Am J Physiol Cell Physiol 287: C834 -C843, 2004; 10.1152/ajpcell.00579.2003.-Skeletal muscle atrophy attributable to muscular inactivity has significant adverse functional consequences. While the initiating physiological event leading to atrophy seems to be the loss of muscle tension and a good deal of the physiology of muscle atrophy has been characterized, little is known about the triggers or the molecular signaling events underlying this process. Decreases in protein synthesis and increases in protein degradation both have been shown to contribute to muscle protein loss due to disuse, and recent work has delineated elements of both synthetic and proteolytic processes underlying muscle atrophy. It is also becoming evident that interactions among known proteolytic pathways (ubiquitin-proteasome, lysosomal, and calpain) are involved in muscle proteolysis during atrophy. Factors such as TNF-␣, glucocorticoids, myostatin, and reactive oxygen species can induce muscle protein loss under specified conditions. Also, it is now apparent that the transcription factor NF-B is a key intracellular signal transducer in disuse atrophy. Transcriptional profiles of atrophying muscle show both up-and downregulation of various genes over time, thus providing further evidence that there are multiple concurrent processes involved in muscle atrophy. The purpose of this review is to synthesize our current understanding of the molecular regulation of muscle atrophy. We also discuss how ongoing work should uncover more about the molecular underpinnings of muscle wasting, particularly that due to disuse. protein synthesis; protein degradation; nuclear factor-B; disuse; unloading; cachexia OVERVIEW Skeletal muscle atrophy is a change that occurs in muscles of adult animals as a result of the conditions of disuse (e.g., immobilization, denervation, muscle unloading), aging, starvation, and a number of disease states (i.e., cachexia). Regardless of the inciting event, skeletal muscle atrophy is characterized by a decrease in protein content, fiber diameter, force production, and fatigue resistance. The different types of conditions producing atrophy imply different types of molecular triggers and signaling pathways for muscle wasting. This review focuses on our current knowledge of the molecules involved in disuse atrophy.Although the molecular aspects of atrophy have received increased attention in the literature, the detailed reviews on disuse atrophy are concerned with the characterization of morphological and physiological changes (12,20,90). With cachexia, there have been multiple reviews, each having a slightly different focus, that summarize work on putative triggers and signaling molecules and on details of the proteolytic processes governing this type of muscle wasting (37,38,57,58). There are no comprehensive reviews, however, on the molecular basis of disuse atrophy with an organized discussion on the whole process, from the potential triggers and signaling molecules to the fi...

DIGE analysis of rat skeletal muscle proteins using nonionic detergent phase extraction of young adult versus aged gastrocnemius tissue

“…Most physiological and histological studies of fibre aging indicate that sarcopenia is due to a multi-factorial pathology. Skeletal muscle aging is associated with a wide variety of cellular, biochemical and physiological alterations, including (i) grouped atrophying fibres, increased numbers of centrally located nuclei and variability in fibre diameter [9], (ii) metabolic alterations [43], (iii) mitochondrial disturbances and an increased susceptibility to apoptosis [44], (iv) a decreased regenerative capacity [45], (v) disturbed luminal ion binding and cycling [46], (vi) excitation-contraction uncoupling [47], (vii) oxidative stress [48], (viii) a blunted cellular stress response [49], (ix) impaired protein synthesis of myofibrillar components [50], ( (x) denervation-associated atrophy [51], (xi) an altered equilibrium of growth factors and hormones involved in fibre maintenance [52], and (xii) a severe decline in contractile efficiency [53]. Our proteomic map of alterations in protein expression in the aqueous versus detergent-extracted fractions from aged muscle agrees with the idea of complex biochemical changes in sarcopenia.…”

Assessment of skeletal muscle proteolysis and the regulatory response to nutrition and exercise

“…It is likely that these four proteolytic systems function in concert to regulate muscle protein degradation in response to nutrition and exercise perturbations (32). For example, FOXO transcription factors regulate UPS activity (29), and FOXO3 is also involved in control of autophagy-related gene expression (33).…”

Estado Nutricional Y Composición Corporal en Escolares De La Serena, Chile

“…El importante déficit de masa muscular encontrado en estos escolares (31,8%), se podría asociar con una inadecuada condición física, como lo informan los resultados de la Evaluación de Educación Física del Sistema de Medición de Calidad de la Educación (SIMCE) del año 2011; donde 93% de la población escolar de 8º básico a nivel nacional presentó esta condición (34), la que llevaría a una inactividad física, ge-nerando una pérdida de masa muscular por desuso y afectaría negativamente la funcionalidad muscular (35), ocasionando cuadros de sarcopenia con consecuencias a nivel metabólico y de riesgo cardiovascular (36)(37)(38). En nuestro país esta situación fue reportada por Burrows y cols, en una población de adolescentes (39).…”