Determinants of Disuse-Induced Skeletal Muscle Atrophy: Exercise and Nutrition Countermeasures to Prevent Protein Loss

Abstract

Summary Muscle atrophy results from a variety of conditions such as disease states, neuromuscular injuries, disuse, and aging. Absence of gravitational loading during spaceflight or long-term bed rest predisposes humans to undergo substantial loss of muscle mass and, consequently, become unfit and/or unhealthy. Disuse-or inactivity-induced skeletal muscle protein loss takes place by differential modulation of proteolytic and synthetic systems. Transcriptional, translational, and posttranslational events are involved in the regulation of protein synthesis and degradation in myofibers, and these regulatory events are known to be responsive to contractile activity. However, regardless of the numerous studies which have been performed, the intracellular signals that mediate skeletal muscle wasting due to muscular disuse are not completely comprehended. Understanding the triggers of atrophy and the mechanisms that regulate protein loss in unloaded muscles may lead to the development of effective countermeasures such as exercise and dietary intervention. The objective of the present review is to provide a window into the molecular processes that underlie skeletal muscle remodeling and to examine what we know about exercise and nutrition countermeasures designed to minimize muscle atrophy. Key Words Skeletal muscle disuse atrophy, microgravity, hindlimb suspension, protein synthesis and degradation, exercise and nutrition countermeasures Because skeletal muscle is the most abundant tissue of the human body, we may hypothesize that decreases in its mass possibly will profoundly impact the wholebody metabolism and ultimately lead to the development of lifestyle-related diseases. In addition, muscle deconditioning (reduced strength, abnormal reflex patterns, increased fatigability) could limit the ability of astronauts to work in space and/or to rapidly egress the spacecraft in an emergency landing ( 1 ). Even though various functional and morphological alterations are noticeable in inactive muscles, decreased protein content has been regarded as the hallmark of skeletal muscle atrophy. Muscle protein can be either gained or lost by relative changes in protein synthesis and degradation rates, which are known to be modulated by contractile activity. Thus, understanding about the molecular regulators of protein turnover during different mechanical loading conditions and their response to specific treatments leads to the likelihood of developing effective countermeasures for preventing disuseinduced muscle wasting.This article provides a review of muscular adaptations to disuse, with emphasis on protein kinetics. We describe first the general aspects of muscle wasting with regard to exposure to actual or ground-based, simulated microgravity and some of the most significant findings that provide evidence for a close connection between skeletal muscle plasticity and protein metabolism. Next, we present a review of the literature in which results of measurements of protein synthesis/ degradation rates during unloading are avail...

Skeletal muscle mass and composition during mammalian hibernation

“…For example, hindlimb suspension (Thomason and Booth, 1990), bed rest (Widrick et al, 1997) and denervation (Hornberger et al, 2001) are all accepted models for investigating decreased activity and disuse atrophy. Commonalities amongst these models are a decrease in muscle mass (Musacchia et al, 1983;Thomason et al, 1987), protein concentration (Bajotto and Shimomura, 2006;Larsson et al, 1996) and fiber size (Pellegrino and Franzini, 1963;Rittweger et al, 2005;Wagatsuma et al, 2011). Most studies also show a conversion from slow to fast fiber types (Boonyarom and Inui, 2006) and a decline in muscle strength (Adams et al, 2003;Larsson et al, 1996;Thomason and Booth, 1990).…”

Atypical fast SERCA1a protein expression in slow myofibers and differential S-nitrosylation prevented by exercise during long term bed rest

“…Skeletal muscle atrophy and diVerential gene expression induced by unloading conditions seem to be particularly pronounced in antigravity muscles comprising high amounts of slow-twitch i.e., type-I myoWbers such as in soleus when compared with the mixed slow/ fast-twitch i.e., type-I/-II myoWber distribution of the vastus lateralis (VL). Although downregulation of myoWber proteins was previously documented in humans (Bajotto and Shimomura 2006), upregulation of several muscle-speciWc genes has been equally described in rodent muscle of unloading models (DiVee et al 1991;Zhu et al 2008) suggesting that muscle atrophy might be the result of an altered balanced between synthesis and degradation of functional muscle proteins.…”

Effects of Nandrolone in the Counteraction of Skeletal Muscle Atrophy in a Mouse Model of Muscle Disuse: Molecular Biology and Functional Evaluation

“…The anti-gravity slow-twitch muscles are the most affected, since in response to reduced neuromuscular activity, they remodel their biochemical and contractile properties toward a faster phenotype [9]. Remodeling involves activation of specific intracellular signaling pathways and consequent genetic re-programming, which may also contribute to the progressive muscle degradation [10]. In principle, muscle atrophy is an adaptive response of the organism to maintain the metabolic and energy homeostasis in adverse conditions.…”