Editorial: Pathophysiological Mechanisms of Sarcopenia in Aging and in Muscular Dystrophy: A Translational Approach

摘要

Sarcopenia and muscular dystrophy are both characterized by the loss of muscle mass and increased intramuscular fibrosis. The two conditions also share several pathophysiological mechanisms, including mitochondrial dysfunction, increased apoptosis, abnormal regulation of autophagy, decline in satellite cell function, increased generation of reactive oxygen species, and alterations of signaling and stress response pathways. Basic science researchers and clinicians working in the areas of sarcopenia and muscular dystrophy in human and animal models contributed to this research topic (Alway et al., 2014 ; Calvani et al., 2014 ; Cesari et al., 2014 ; De Palma et al., 2014 ; Gattazzo et al., 2014 ; Harris-Love et al., 2014 ; Hepple, 2014 ; Holland et al., 2014 ; Holmberg et al., 2014 ; Jungbluth and Gautel, 2014 ; Kern et al., 2014 ; La Rovere et al., 2014 ; Lim et al., 2014 ; Malatesta et al., 2014 ; Marzetti et al., 2014 ; Merlini et al., 2014 ; Palmio and Udd, 2014 ; Pozzobon et al., 2014 ; Raz and Raz, 2014 ; Rudolf et al., 2014 ; Sabatelli et al., 2014 ; Sakuma et al., 2014 ; Sanchis-Gomar et al., 2014 ; Tamaki et al., 2014 ; Toni et al., 2014 ; Zulian et al., 2014 ; Krause, 2015 ). The aim of this cross-fertilization was to accelerate our understanding of the mechanisms involved in aging and dystrophic sarcopenia and to explore the therapeutic potential of various intervention modalities. Since its first “official” appreciation back in 1989 (Rosenberg, 1989 ), sarcopenia has attracted great research interest. The intimate relationship between muscle loss and advancing age, evident across multiple species, has led researchers to consider sarcopenia as a paradigm for exploring the aging process as a whole. Sarcopenia is indeed envisioned as a biomarker of aging, able to distinguish, at the clinical level, biological from chronological age (Fisher, 2004 ). This view is supported by the association reported between sarcopenia and the length of telomeres in peripheral blood mononuclear cells (PBMCs), a popular biological marker of senescence (Marzetti et al., 2014 ). This relationship seemed to be driven mainly by the muscle mass, which suggests the existence of a common pathogenic basis for muscle atrophy and telomere attrition. No significant association was found between PBMC telomere length and muscle strength or function parameters, pointing at distinct pathogenic mechanisms underlying the quantitative and qualitative dimensions of sarcopenia. Decreased number and impaired function of satellite cells, the major stem cell population responsible for skeletal muscle regeneration during adulthood, are considered to be major the mechanisms contributing to sarcopenia (Chakkalakal and Brack, 2012 ). Along with changes in systemic factors and the environmental cues provided by satellite cells, oxidative stress that characterizes the aged muscle contributes to impairing satellite cells responses to exercise, disuse, and rehabilitation. Some nutritional intervention may improve satellite cell function in aged muscles; however, the effect of nutraceuticals on satellite cell function in the context of sarcopenia is not yet well established. Alway et al. ( 2014 ) provided an overview on the contribution of satellite cell dysfunction to sarcopenia. The authors also reviewed data from preclinical studies showing that the administration of specific nutraceuticals (resveratrol, green tea catechins, and β-hydroxy-β-methylbutyrate) may improve satellite cell function, thereby mitigating sarcopenia and promoting muscle recovery after disuse. Most studies aimed at testing potential therapeutic approaches targeting satellite cells in muscle diseases have been conducted in small mammalian models. Though, our knowledge of muscle regeneration in large animal models, such as dogs, remains relatively limited. La Rovere et al. ( 2014 ) investigated the myogenic potential of satellite cells isolated from somite- and presomite-derived muscles of young and aged dogs, as well as from Golden Retrievers affected by muscular dystrophy. Satellite cells obtained from the two canine sources showed different proliferation and differentiation rates. Indeed, those isolated from presomitic-derived muscle showed higher telomerase activity and stronger stem cell potential, whereas satellite cells obtained from somitic-derived muscle expressed early and late myogenic markers, resulting in more efficient cell differentiation. Interestingly, expression profiling of muscle-specific miRNAs revealed a unique epigenetic signature in Golden Retriever muscular dystrophy, suggesting that miR-206 might represent a potential target for therapy. Satellite cell dysfunction is involved in collagen VI-related myopathies. Collagen VI is an extracellular matrix protein, essential for muscle homeostasis (Bonaldo et al., 1998 ). Mutations in the gene encoding for collagen VI cause different forms of inherited myopathies and congenital muscular dystrophies. Studies car