Effects of aging, exercise, and disease on force transfer in skeletal muscle

Abstract

Hughes DC, Wallace MA, Baar K. Effects of aging, exercise, and disease on force transfer in skeletal muscle. Am J Physiol Endocrinol Metab 309: E1-E10, 2015. First published May 12, 2015; doi:10.1152/ajpendo.00095.2015.-The loss of muscle strength and increased injury rate in aging skeletal muscle has previously been attributed to loss of muscle protein (cross-sectional area) and/or decreased neural activation. However, it is becoming clear that force transfer within and between fibers plays a significant role in this process as well. Force transfer involves a secondary matrix of proteins that align and transmit the force produced by the thick and thin filaments along muscle fibers and out to the extracellular matrix. These specialized networks of cytoskeletal proteins aid in passing force through the muscle and also serve to protect individual fibers from injury. This review discusses the cytoskeleton proteins that have been identified as playing a role in muscle force transmission, both longitudinally and laterally, and where possible highlights how disease, aging, and exercise influence the expression and function of these proteins. force transmission; dystrophin-glycoprotein complex; injury; aging ON AVERAGE, HUMANS LOSE AROUND 45% of their muscle mass between their mid-20s and 80s (47,70,71). This loss in muscle mass in the absence of disease is known as sarcopenia (60). The decline in muscle mass is accompanied by, but cannot fully explain, a rapid loss in muscle strength (64). The loss in muscle strength has previously been investigated from the perspectives of loss of muscle protein mass (cross-sectional area) and decreased neural activation. A third possibility, impaired force transfer, has received the least attention in relation to aging, exercise, and disease (66,90,102). However, recent advances in our understanding of this process suggest that force transfer plays an important role in muscle strength and injury prevention, and this fact is the focus of this review. Force TransferOver 60 years ago, Andrew Huxley and his students used electron microscopy to show that during muscle contraction the I-band (containing the thin filament) shortened whereas the A-band (containing the thick filament) remained a constant length (39). Their famous "sliding theory of muscle contraction" provided an image of a muscle shortening end to end as the A-bands drew closer together. Implied in this model is that force is transferred in a longitudinal manner as a result of sarcomere shortening. However, a deeper consideration of this model requires that there be a secondary matrix of proteins that are not visible to the electron microscope, proteins that transmit the force produced by the thick and thin filaments along the muscle fiber to the tendons. These specialized networks of cytoskeletal proteins transmit force through the muscle to the tendon and also serve to protect individual fibers from injury.An important structure in these networks is the "costamere", which connects the sarcolemma with the contractile appar...

Molecular Regulation of Exercise-Induced Muscle Fiber Hypertrophy

“…The DGC, a complex of numerous structural and signaling proteins linking the contractile apparatusto the myofiber membrane (sarcolemma), is critical for maintaining myofiber integrity. Indeed, lack of the primary DGC protein dystrophin, as seen in Duchenne muscular dystrophy, causes irreparable myofiber damage, and declining levels of dystrophin in aging muscle increase susceptibility to damage (Hughes et al 2015). Interestingly, dystrophin itself is capable of mediating signals relevant to muscle hypertrophy (Acharyya et al 2005).…”

Alterations in the muscle force transfer apparatus in aged rats during unloading and reloading: impact of microRNA‐31

“…These two costameric complexes work together to provide a tight connection between the sarcomere and the ECM (Hughes et al . ). In fact, in animals that lack dystrophin the α7 integrin is upregulated, and when both proteins are knocked out, the result is a more severe muscular dystrophy (Rooney et al .…”

“…; Hughes et al . ). There is evidence that contractile protein oxidation increases with age; however, whether this contributes to the loss of muscle quality remains equivocal (Thompson et al .…”

Shear strain rate from phase contrast velocity encoded MRI: Application to study effects of aging in the medial gastrocnemius muscle

“…One potential determinant of age‐related loss of muscle force that has not been investigated in depth is the remodeling of the extracellular matrix (ECM) and its functional consequences . Several studies have emphasized the importance of force transmission pathways: longitudinal transmission of force via the myotendinous junction and lateral transmission of force mediated by the ECM via myofascical pathways . Impairment in lateral transmission pathways with age have been demonstrated in aging rodents and has been linked to the remodeling of the ECM .…”