Changes in communication between muscle stem cells and their environment with aging

Aging is associated with both muscle weakness and a loss of muscle mass, contributing towards overall frailty in the elderly. Aging skeletal muscle is also characterised by a decreasing efficiency in repair and regeneration, together with a decline in the number of adult stem cells. Commensurate with this are general changes in whole body endocrine signalling, in local muscle secretory environment, as well as in intrinsic properties of the stem cells themselves. The present review discusses the various mechanisms that may be implicated in these age-associated changes, focusing on aspects of cell-cell communication and long-distance signalling factors, such as levels of circulating growth hormone, IL-6, IGF1, sex hormones, and inflammatory cytokines. Changes in the local environment are also discussed, implicating IL-6, IL-4, FGF-2, as well as other myokines, and processes that lead to thickening of the extra-cellular matrix. These factors, involved primarily in communication, can also modulate the intrinsic properties of muscle stem cells, including reduced DNA accessibility and repression of specific genes by methylation. Finally we discuss the decrease in the stem cell pool, particularly the failure of elderly myoblasts to re-quiesce after activation, and the consequences of all these changes on general muscle homeostasis

CellWhere: graphical display of interaction networks organized on subcellular localizations

International audienceGiven a query list of genes or proteins, CellWhere produces an interactive graphical display that mimics the structure of a cell, showing the local interaction network organized into subcellular locations. This user-friendly tool helps in the formulation of mechanistic hypotheses by enabling the experimental biologist to explore simultaneously two elements of functional context: (i) protein subcellular localization and (ii) protein–protein interactions or gene functional associations. Subcellular localization terms are obtained from public sources (the Gene Ontology and UniProt—together containing several thousand such terms) then mapped onto a smaller number of CellWhere localizations. These localizations include all major cell compartments, but the user may modify the mapping as desired. Protein–protein interaction listings, and their associated evidence strength scores, are obtained from the Mentha interactome server, or power-users may upload a pre-made network produced using some other interactomics tool. The Cytoscape.js JavaScript library is used in producing the graphical display. Importantly, for a protein that has been observed at multiple subcellular locations, users may prioritize the visual display of locations that are of special relevance to their research domain. CellWhere is at http://cellwhere-myology.rhcloud.com

Intramuscular sex steroid hormones are associated with skeletal muscle strength and power in women with different hormonal status

Peer reviewe

Adenylosuccinic acid therapy ameliorates murine Duchenne Muscular Dystrophy

International audienceArising from the ablation of the cytoskeletal protein dystrophin, Duchenne Muscular Dystrophy (DMD) is a debilitating and fatal skeletal muscle wasting disease underpinned by metabolic insufficiency. The inability to facilitate adequate energy production may impede calcium (Ca2+) buffering within, and the regenerative capacity of, dystrophic muscle. Therefore, increasing the metabogenic potential could represent an effective treatment avenue. The aim of our study was to determine the efficacy of adenylosuccinic acid (ASA), a purine nucleotide cycle metabolite, to stimulate metabolism and buffer skeletal muscle damage in the mdx mouse model of DMD. Dystrophin-positive control (C57BL/10) and dystrophin-deficient mdx mice were treated with ASA (3000 µg.mL-1) in drinking water. Following the 8-week treatment period, metabolism, mitochondrial density, viability and superoxide (O2-) production, as well as skeletal muscle histopathology, were assessed. ASA treatment significantly improved the histopathological features of murine DMD by reducing damage area, the number of centronucleated fibres, lipid accumulation, connective tissue infiltration and Ca2+ content of mdx tibialis anterior. These effects were independent of upregulated utrophin expression in the tibialis anterior. ASA treatment also increased mitochondrial viability in mdx flexor digitorum brevis fibres and concomitantly reduced O2- production, an effect that was also observed in cultured immortalised human DMD myoblasts. Our data indicates that ASA has a protective effect on mdx skeletal muscles

Optimized method for extraction of exosomes from human primary muscle cells

International audienceSkeletal muscle is increasingly considered an endocrine organ secreting myokines and extracellular vesicles (exosomes and microvesicles), which can affect physiological changes with an impact on different pathological conditions, including regenerative processes, aging, and myopathies. Primary human myoblasts are an essential tool to study the muscle vesicle secretome. Since their differentiation in conditioned media does not induce any signs of cell death or cell stress, artefactual effects from those processes are unlikely. However, adult human primary myoblasts senesce in long-term tissue culture, so a major technical challenge is posed by the need to avoid artefactual effects resulting from pre-senescent changes. Since these cells should be studied within a strictly controlled pre-senescent division count (30 times fewer differentiated myoblasts than what is required for the ultracentrifugation method. In addition, exosomes could still be integrated into recipient cells such as human myotubes or iPSC-derived motor neurons. Modified polymer-based precipitation combined with extra washing steps optimizes exosome yield from a lower number of differentiated myoblasts and less conditioned medium, avoiding senescence and allowing the execution of multiple experiments without exhausting the proliferative capacity of the myoblasts