Abstract
Primary abnormalities in the dystrophin gene cause X-linked muscular dystrophy, a highly progressive muscle wasting disorder of childhood. A spontaneous animal model of Duchenne muscular dystrophy is the mdx mouse, which presents a highly interesting phenotype that exhibits considerable variations in the degree of fiber degeneration in different subtypes of muscles. The idea that aging exacerbates the dystrophic mdx phenotype, as previously indicated by a large number of biochemical and cell biological studies, was clearly confirmed by comparative muscle proteomics. Here we outline recent findings of age-dependent changes in the dystrophin-deficient muscle proteome and contrast these results with the previously established proteomic profile of sarcopenic muscle. Besides comparable perturbations of various biochemical functions, especially striking are similarities in the cellular stress response associated with a drastic up-regulation of small αB-crystallin-like heat shock proteins. Hence, the comparison of large-scale proteomic data sets of natural muscle aging with dystrophic sarcopenia promises to shed light on the differential effect of sarcopenia of old age vs. senescent abnormalities on a mutant dystrophic background.
Highlights
A high degree of load bearing and the continuous strain of excitation-contraction-relaxation cycles exert considerable physical tension on the peripheral structures of muscle fibers
In Duchenne muscular dystrophy, primary genetic abnormalities in the dystrophin gene cause the loss of the fulllength Dp427 isoform of this membrane cytoskeletal protein (Hoffman et al, 1987) and the drastic reduction in all dystrophinassociated glycoproteins (Ohlendieck et al, 1993)
In this Perspective Article, the age-related exacerbation of the dystrophic phenotype is discussed and new pathobiochemical insights into dystrophinopathy outlined as revealed from the proteomic profiling of senescent mdx mouse muscles
Summary
Reviewed by: Ali Mobasheri, University of Surrey, UK John James Mackrill, University College Cork, Ireland. Primary abnormalities in the dystrophin gene cause X-linked muscular dystrophy, a highly progressive muscle wasting disorder of childhood. A spontaneous animal model of Duchenne muscular dystrophy is the mdx mouse, which presents a highly interesting phenotype that exhibits considerable variations in the degree of fiber degeneration in different subtypes of muscles. The idea that aging exacerbates the dystrophic mdx phenotype, as previously indicated by a large number of biochemical and cell biological studies, was clearly confirmed by comparative muscle proteomics. We outline recent findings of age-dependent changes in the dystrophin-deficient muscle proteome and contrast these results with the previously established proteomic profile of sarcopenic muscle. The comparison of large-scale proteomic data sets of natural muscle aging with dystrophic sarcopenia promises to shed light on the differential effect of sarcopenia of old age vs senescent abnormalities on a mutant dystrophic background
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