Tissue-specific methylomic responses to a lifestyle intervention in older adults associate with metabolic and physiological health improvements.

Across the lifespan, diet and physical activity profiles substantially influence immunometabolic health. DNA methylation, as a tissue-specific marker sensitive to behavioral change, may mediate these effects through modulation of transcription factor binding and subsequent gene expression. Despite this, few human studies have profiled DNA methylation and gene expression simultaneously in multiple tissues or examined how molecular levels react and interact in response to lifestyle changes.

Different outcomes of endurance and resistance exercise in skeletal muscles of Oculopharyngeal muscular dystrophy.

Background: Exercise is widely considered to have beneficial impact on skeletal muscle aging. In addition, there are also several studies demonstrating a positive effect of exercise on muscular dystrophies. Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant inherited neuromuscular disorder caused by mutations in the PAPBN1 gene.

Our journey with François Gros.

Gillian Butler-Browne began working on muscle at the Institut Pasteur in the laboratory of François Gros in 1978. She characterized the expression profile of different myosin isoforms during both human and rodent development. Vincent Mouly joined this laboratory for his PhD in 1982, and defined the different populations of myoblasts appearing during development in birds and then in humans.

T cell biology in neuromuscular disorders: a focus on Duchenne Muscular Dystrophy and Amyotrophic Lateral Sclerosis.

Growing evidence demonstrates a continuous interaction between the immune system, the nerve and the muscle in neuromuscular disorders of different pathogenetic origins, such as Duchenne Muscular Dystrophy (DMD) and Amyotrophic Lateral Sclerosis (ALS), the focus of this review. Herein we highlight the complexity of the cellular and molecular interactions involving the immune system in neuromuscular disorders, as exemplified by DMD and ALS. We describe the distinct types of cell-mediated interactions, such as cytokine/chemokine production as well as cell-matrix and cell-cell interactions between T lymphocytes and other immune cells, which target cells of the muscular or nervous tissues.

[Nuclear aggregates in oculopharyngeal muscular dystrophy].

Oculopharyngeal muscular dystrophy (OPMD) is one of the diseases related to pathological expansions of trinucleotides. Its pathogenesis remains unclear although the presence of aggregates within the nuclei of the muscle fiber seems to play an important role. The basic research studies presented here help understand their composition and their deleterious role.

Update on anti-fibrotic pharmacotherapies in skeletal muscle disease.

Fibrosis, defined as an excessive accumulation of extracellular matrix, is the end point of a defective regenerative process, unresolved inflammation and/or chronic damage. Numerous muscle disorders (MD) are characterized by high levels of fibrosis associated with muscle wasting and weakness. Fibrosis alters muscle homeostasis/regeneration and fiber environment and may interfere with gene and cell therapies.

Muscle fibro-adipogenic progenitors from a single-cell perspective: Focus on their "virtual" secretome.

Skeletal muscle is a highly plastic tissue composed of a number of heterogeneous cell populations that, by interacting and communicating with each other, participate to the muscle homeostasis, and orchestrate regeneration and repair in healthy and diseased conditions. Although muscle regeneration relies on the activity of muscle stem cells (MuSCs), many other cellular players such as inflammatory, vascular and tissue-resident mesenchymal cells participate and communicate with MuSCs to sustain the regenerative process. Among them, Fibro-Adipogenic Progenitors (FAPs), a muscle interstitial stromal population, are crucial actors during muscle homeostasis and regeneration, interacting with MuSCs and other cellular players and dynamically producing and remodelling the extra-cellular matrix.

Assessment of PABPN1 nuclear inclusions on a large cohort of patients and in a human xenograft model of oculopharyngeal muscular dystrophy.

Oculopharyngeal muscular dystrophy (OPMD) is a rare muscle disease characterized by an onset of weakness in the pharyngeal and eyelid muscles. The disease is caused by the extension of a polyalanine tract in the Poly(A) Binding Protein Nuclear 1 (PABPN1) protein leading to the formation of intranuclear inclusions or aggregates in the muscle of OPMD patients. Despite numerous studies stressing the deleterious role of nuclear inclusions in cellular and animal OPMD models, their exact contribution to human disease is still unclear.

Myostatin in idiopathic inflammatory myopathies: Serum assessment and disease activity.

Aims: In idiopathic inflammatory myopathies (IIM), disease activity is difficult to assess, and IIM may induce severe muscle damage, especially in immune-mediated necrotising myopathies (IMNM) and inclusion body myositis (IBM). We hypothesise that myostatin, a negative regulator of muscle mass, could be a new biomarker of disease activity and/or muscle damage.

Methods: Prospective assessment of myostatin protein level in 447 IIM serum samples (dermatomyositis [DM], n = 157; IBM, n = 72; IMNM, n = 125; and antisynthetase syndrome [ASyS], n = 93) and 59 healthy donors (HD) was performed by ELISA.

A negative feedback loop between fibroadipogenic progenitors and muscle fibres involving endothelin promotes human muscle fibrosis.

Background: Fibrosis is defined as an excessive accumulation of extracellular matrix (ECM) components. Many organs are subjected to fibrosis including the lung, liver, heart, skin, kidney, and muscle. Muscle fibrosis occurs in response to trauma, aging, or dystrophies and impairs muscle function.

Muscle cells of sporadic amyotrophic lateral sclerosis patients secrete neurotoxic vesicles.

Background: The cause of the motor neuron (MN) death that drives terminal pathology in amyotrophic lateral sclerosis (ALS) remains unknown, and it is thought that the cellular environment of the MN may play a key role in MN survival. Several lines of evidence implicate vesicles in ALS, including that extracellular vesicles may carry toxic elements from astrocytes towards MNs, and that pathological proteins have been identified in circulating extracellular vesicles of sporadic ALS patients. Because MN degeneration at the neuromuscular junction is a feature of ALS, and muscle is a vesicle-secretory tissue, we hypothesized that muscle vesicles may be involved in ALS pathology.

Zika virus disrupts gene expression in human myoblasts and myotubes: Relationship with susceptibility to infection.

The tropism of Zika virus (ZIKV) has been described in the nervous system, blood, placenta, thymus, and skeletal muscle. We investigated the mechanisms of skeletal muscle susceptibility to ZIKV using an in vitro model of human skeletal muscle myogenesis, in which myoblasts differentiate into myotubes. Myoblasts were permissive to ZIKV infection, generating productive viral particles, while myotubes controlled ZIKV replication.

Challenges in cell transplantation for muscular dystrophy.

For decades now, cell transplantation has been considered a possible therapeutic strategy for muscular dystrophy, but failures have largely outnumbered success or at least encouraging outcomes. In this review we will briefly recall the history of cell transplantation, discuss the peculiar features of skeletal muscle, and dystrophic skeletal muscle in particular, that make the procedure complicated and inefficient. As there are many recent and exhaustive reviews on the various myogenic cell types that have been or will be transplanted, we will only briefly describe them and refer the reader to these reviews.

Myogenic Cell Transplantation in Genetic and Acquired Diseases of Skeletal Muscle.

This article will review myogenic cell transplantation for congenital and acquired diseases of skeletal muscle. There are already a number of excellent reviews on this topic, but they are mostly focused on a specific disease, muscular dystrophies and in particular Duchenne Muscular Dystrophy. There are also recent reviews on cell transplantation for inflammatory myopathies, volumetric muscle loss (VML) (this usually with biomaterials), sarcopenia and sphincter incontinence, mainly urinary but also fecal.

Age-related alterations in muscle architecture are a signature of sarcopenia: the ultrasound sarcopenia index.

Background: The assessment of muscle mass is a key determinant of the diagnosis of sarcopenia. We introduce for the first time an ultrasound imaging method for diagnosing sarcopenia based on changes in muscle geometric proportions.

Methods: Vastus lateralis muscle fascicle length (Lf) and thickness (Tm) were measured at 35% distal femur length by ultrasonography in a population of 279 individuals classified as moderately active elderly (MAE), sedentary elderly (SE) (n = 109), mobility impaired elderly (MIE) (n = 43), and in adult young controls (YC) (n = 60).

Cross-talk between motor neurons and myotubes via endogenously secreted neural and muscular growth factors.

Neuromuscular junction (NMJ) research is vital to advance the understanding of neuromuscular patho-physiology and development of novel therapies for diseases associated with NM dysfunction. In vivo, the micro-environment surrounding the NMJ has a significant impact on NMJ formation and maintenance via neurotrophic and differentiation factors that are secreted as a result of cross-talk between muscle fibers and motor neurons. Recently we showed the formation of functional NMJs in vitro in a co-culture of immortalized human myoblasts and motor neurons from rat-embryo spinal-cord explants, using a culture medium free from serum and neurotrophic or growth factors.

Lamin-Related Congenital Muscular Dystrophy Alters Mechanical Signaling and Skeletal Muscle Growth.

Laminopathies are a clinically heterogeneous group of disorders caused by mutations in the gene, which encodes the nuclear envelope proteins lamins A and C. The most frequent diseases associated with mutations are characterized by skeletal and cardiac involvement, and include autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy type 1B, and -related congenital muscular dystrophy (-CMD). Although the exact pathophysiological mechanisms responsible for -CMD are not yet understood, severe contracture and muscle atrophy suggest that mutations may impair skeletal muscle growth.

Nitric Oxide (NO) and Duchenne Muscular Dystrophy: NO Way to Go?

The discordance between pre-clinical success and clinical failure of treatment options for Duchenne Muscular Dystrophy (DMD) is significant. The termination of clinical trials investigating the phosphodiesterase inhibitors, sildenafil and tadalafil (which prolong the second messenger molecule of nitric oxide (NO) signaling), are prime examples of this. Both attenuated key dystrophic features in the mouse model of DMD yet failed to modulate primary outcomes in clinical settings.

Crosstalk Between Innate and T Cell Adaptive Immunity With(in) the Muscle.

Growing evidence demonstrates a continuous interaction between the immune system and the skeletal muscle in inflammatory diseases of different pathogenetic origins, in dystrophic conditions such as Duchenne Muscular Dystrophy as well as during normal muscle regeneration. Although one component of the innate immunity, the macrophage, has been extensively studied both in disease conditions and during cell or gene therapy strategies aiming at restoring muscular functions, much less is known about dendritic cells and their primary immunological targets, the T lymphocytes. This review will focus on the dendritic cells and T lymphocytes (including effector and regulatory T-cells), emphasizing the potential cross talk between these cell types and their influence on the structure and function of skeletal muscle.

A Novel Bioengineered Functional Motor Unit Platform to Study Neuromuscular Interaction.

Background: In many neurodegenerative and muscular disorders, and loss of innervation in sarcopenia, improper reinnervation of muscle and dysfunction of the motor unit (MU) are key pathogenic features. studies of MUs are constrained due to difficulties isolating and extracting functional MUs, so there is a need for a simplified and reproducible system of engineered MUs.

Objective: to develop and characterise a functional MU model , permitting the analysis of MU development and function.

Differentiation-dependent susceptibility of human muscle cells to Zika virus infection.

Muscle cells are potential targets of many arboviruses, such as Ross River, Dengue, Sindbis, and chikungunya viruses, that may be involved in the physiopathological course of the infection. During the recent outbreak of Zika virus (ZIKV), myalgia was one of the most frequently reported symptoms. We investigated the susceptibility of human muscle cells to ZIKV infection.

Optimized method for extraction of exosomes from human primary muscle cells.

Skeletal 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.