Muscle damage and muscle remodeling : no pain , no gain ? Kyle

INTRODUCTION Skeletal muscle retains a large degree of phenotypic plasticity throughout the lifetime of an individual, allowing muscle to respond adaptively to changes in both the nature and intensity of muscle use. Hence, repeated bouts of resistance exercise produce compensatory growth (hypertrophy) of skeletal muscle, even late in life (Drummond et al., 2008), characterized by an increase in the cross-sectional area of individual muscle fibers as well as the volume of whole muscle. Because force production is a function of the crosssectional area of a muscle, the consequence of increased muscle mass is greater force production (strength). Although muscle growth in response to resistance exercise has long been recognized, it is only now that the details of the mechanisms underlying this response are becoming clear. A key element in muscle growth is the regulation of skeletal muscle protein synthesis, which involves several intracellular signaling pathways (Nadar et al., 2002; Rennie et al., 2004). In particular, the anabolic mediator and myogenic growth factor insulin-like growth factor 1 (IGF-1) is known to be upregulated during muscle hypertrophy. IGF-1 stimulation alone has been shown to be sufficient for induction of skeletal muscle hypertrophy (Coleman et al., 1995; Musaro et al., 2001); moreover, a musclespecific isoform of IGF-1 – IGF-1Ea – has been described as contributing to muscle regeneration (Chakravathy et al., 2000; Rotwein et al., 1986; Yang et al., 1996). This study was designed to investigate whether muscle hypertrophy is possible in the absence of the symptoms of damage. This issue becomes most crucial for those individuals who are exercise limited or exercise intolerant owing to existing cardiopulmonary pathologies. Can interventions be designed for these individuals that do not involve damage sufficient to initiate a repair response (and hence a potentially harmful inflammatory response) as a precursor to muscle hypertrophy? Since Goldberg and colleagues (Goldberg et al., 1975) first proposed that the development of muscle force is the crucial event in initiating muscle growth in mammals, efforts have been made to identify the ‘optimal’ exercise regime to maximize muscle force production and the resultant hypertrophy and improved performance. Because the greatest magnitude of muscle force production occurs during lengthening (eccentric) contractions, high-force eccentric exercise might be the most powerful stimulus to induce hypertrophy (Hortobagyi, 2003; LaStayo et al., 2000; LaStayo et al., 2003). Furthermore, this kind of muscle use often results in an initial damaging bout of exercise, which is often thought to be a prerequisite for the initiation of muscle hypertrophy (Evans and Cannon, 1991; Folland et al., 2002; Goldspink, 2003; Hawke and Garry, 2001; Smith et al., 1999). Indeed, high-force lengthening (eccentric) forces often result in muscle ultrastructural damage (Ebbeling and Clarkson, 1989; Newham, 1988) – however, these need not cause muscle damage (Crameri et al., 2007). In this study, The Journal of Experimental Biology 214, 674-679 © 2011. Published by The Company of Biologists Ltd doi:10.1242/jeb.050112