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Duchenne muscular dystrophy (DMD) is a life-limiting, neuromuscular disorder that causes progressive, severe muscle wasting in boys and young men. Although there is no cure, scientists and clinicians can leverage the fact that slower, more oxidative skeletal muscle fibers possess an enhanced degree of resistance to the dystrophic pathology relative to their faster, more glycolytic counterparts, and can thus use this knowledge when investigating novel therapeutic avenues. Several factors have been identified as powerful regulators of muscle plasticity. Some proteins, such as calcineurin, peroxisome proliferator-activated receptor (PPAR) γ coactivator lα (PGC-lα), PPARβ/δ, and AMP-activated protein kinase (AMPK), when chronically stimulated in animal models, remodel skeletal muscle toward the slow, oxidative myogenic program, whereas others, such as receptor-interacting protein 140 (RIP140) and E2F transcription factor 1 (E2F1), repress this phenotype. Recent studies demonstrating that pharmacologic and physiological activation of targets that shift dystrophic muscle toward the slow, oxidative myogenic program provide appreciable molecular and functional benefits. This review surveys the rationale behind, and evidence for, the study of skeletal muscle plasticity in preclinical models of DMD and highlights the potential therapeutic opportunities in advancing a strategy focused on remodeling skeletal muscle in patients with DMD toward the slow, oxidative phenotype [ABSTRACT FROM AUTHOR]

Reduced plasticity of senescent skeletal muscle may be due to an attenuated signaling response to contractions. The intent of the present study was to determine whether aging affects signaling pathways involved in mitochondrial biogenesis in response to a single bout of contractile activity (CA). Acute stimulation (1 Hz, 5 min) of the tibialis anterior (TA) resulted in a significantly greater rate of fatigue in 36 month (mo) relative to 6 mo F344XBN rats. To investigate fiber type-specific signaling, the TA was sectioned into red (RTA) and white (WTA) portions, possessing 2.5-fold differences in mitochondrial content. The CA-mediated activation of p38, MKK3/6, CaMK11 and AMPK signaling was assessed. In general, CA-evoked kinase phosphorylation was greater in RTA compared to WTA in both age groups, p38 activation was similar in RTA from 6 and 36 mo groups, however in WTA, the response was 2-fold greater in muscle from 6, relative to 36 mo animals. CA also increased MKK3/6 phosphorylation, the upstream regulator of p38, however the magnitude was 70-80% higher in RTA and WTA of 6, compared to 36 mo rats. Contraction-induced CaMKII phosphorylation was 40% higher in both fiber types in muscle from 6 relative to 36 mo animals. AMPK was not responsive to 1 Hz CA at either age. Thus, CA-induced signaling to mitochondrial biogenesis is reduced in aging muscle, but the extent of the attenuation depends in part on mitochondrial content. [ABSTRACT FROM AUTHOR]