Exercise-induced muscle injury and the subsequent release of Damage-Associated Molecular Patterns (DAMP) result in soreness and inflammation. Dietary supplements may accelerate the rate of recovery by supporting resolution of inflammation. The purpose of this study was to determine if methylsulfonylmethane (MSM) supplementation (30 d prior to exercise and during recovery) altered mRNA expression in LPS-exposed blood leukocytes after a bout of downhill running. Exercise consisted of 60 min of downhill running (−15% grade). Blood (baseline, pre-exercise, 4, 24, 48, and 72 h post-exercise) was diluted (1:10) and combined with LPS (20 µg/mL) for 24 h. Total RNA was isolated from leukocytes and analyzed for 574 immune-associated mRNA (Nanostring nCounter; ROSALIND.BIO). Data were expressed as log2 fold change from baseline for each condition (MSM and placebo). Compared to placebo, MSM supplementation was associated with an improved inflammation response (15 mRNA) and viral immune response (2 mRNA). The largest number of changes were found at 4 and 24 h post-exercise. The key finding in the present study is that MSM supplementation can improve inflammation management and the innate immune response after exercise. Full article

It is well known that muscular dystrophy disease severity is controlled by genetic modifiers. The expectation is that by identifying these modifiers, we can illuminate additional therapeutic targets with which to combat the disease. To this end we have been investigating the MRL mouse strain, which is highly resistant to muscular dystrophy-mediated fibrosis. The MRL mouse strain contains two mitochondrial-encoded, naturally occurring heteroplasmies: T3900C in tRNA-Met, and variable adenine insertions at 9821 in tRNA-Arg. Heteroplasmies are mitochondrial mutations that are variably present in a cell’s mitochondria. Therefore, MRL cells can contain 0 to 100% of each mitochondrial mutation. We have chosen the severely affected ϒ-sarcoglycan (Sgcg–/–) deficient mice on the DBA2/J background as our muscular dystrophy model to demonstrate the effects of these mitochondrial heteroplasmies on disease severity. Mice from the (Sgcg–/–) DBA2/J (D) and wildtype MRL (M) strains were crossed for more than 10 generations to establish two separate, pure breeding mouse lines: Sgcg+/–Nuc^DMito^%M and Sgcg+/–Nuc^MMito^%M. The Sgcg–/– mice from these separate lines were analyzed at 8 weeks old for membrane permeability, hydroxyproline content, pAMPK content, fibronectin content, and percentage of each heteroplasmy. We have identified that the MRL mitochondrial mutation T3900C confers a portion of the fibrosis resistance identified in the MRL mouse strain. These results have been extended to significantly correlate increased MRL mitochondria with increased pAMPK and decreased muscular dystrophy fibrosis. The beneficial mechanisms controlled by the MRL mitochondria will be discussed. We are establishing metabolic aspects of muscular dystrophy pathogenesis. These metabolic pathways will now be investigated for therapeutic targets. Full article

Musculoskeletal health is directly linked to independence and longevity, but disease and aging impairs muscle mass and health. Complete repair after a pathological or physiological muscle injury is critical for maintaining muscle function, yet muscle repair is compromised after disuse, or in conditions such as metabolic diseases, cancer, and aging. Regeneration of damaged tissue is critically dependent upon achieving the optimal function of satellite cells (muscle stem cells, MSCs). MSC remodeling in muscle repair is highly dependent upon its microenvironment, and metabolic health of MSCs, which is dependent on the functional capacity of their mitochondria. Muscle repair is energy demanding and mitochondria provide the primary source for energy production during regeneration. However, disease and aging induce mitochondrial dysfunction, which limits energy production during muscle regeneration. Nevertheless, the role of mitochondria in muscle repair likely extends beyond the production of ATP and mitochondria could provide potentially important regulatory signaling to MSCs during repair from injury. The scope of current research in muscle regeneration extends from molecules to exosomes, largely with the goal of understanding ways to improve MSC function. This review focuses on the role of mitochondria in skeletal muscle myogenesis/regeneration and repair. A therapeutic strategy for improving muscle mitochondrial number and health will be discussed as a means for enhancing muscle regeneration. Highlights: (a). Mitochondrial dysfunction limits muscle regeneration; (b). Muscle stem cell (MSC) function can be modulated by mitochondria; (c). Enhancing mitochondria in MSCs may provide a strategy for improving muscle regeneration after an injury. Full article

The diagnosis of primary mitochondrial myopathy is often delayed by years due to non-specific clinical symptoms as well as variable testing of mitochondrial disorders. The aim of this review is to summarize and discuss the collective findings and novel insights regarding the diagnosing, testing, and clinical presentation of primary mitochondrial myopathy (PMM). PMM results from a disruption of the oxidative phosphorylation (OXPHOS) chain in mitochondria due to mutations in mitochondrial DNA (mtDNA) or nuclear DNA (nDNA). Although there are many named syndromes caused by mitochondrial mutations, this review will focus on PMM, which are mitochondrial disorders mainly affecting, but not limited to, the skeletal muscle. Clinical presentation may include muscle weakness, exercise intolerance, myalgia, and rhabdomyolysis. Although skeletal muscle and respiratory function are most frequently affected due to their high energy demand, multisystem dysfunction may also occur, which may lead to the inclusion of mitochondrial myopathies on the differential. Currently, there are no effective disease-modifying treatments, and treatment programs typically only focus on managing the symptomatic manifestations of the disease. Although the field has a large unmet need regarding treatment options, diagnostic pathways are better understood and can help shorten the diagnostic journey to aid in disease management and clinical trial enrollment. Full article