Reprogramming of Myeloid Responses to Volumetric Muscle Loss via Engineered Protein Nanoparticles.

The acute loss of muscle tissue from trauma or surgery or volumetric muscle loss (VML) is a significant injury that results in chronic and sustained inflammatory responses that in turn impinge on recovery of neuromuscular function. Understanding and manipulating the immune response to volumetric muscle loss thus hold promise for limiting tissue damage and improving regenerative outcomes. Herein, we analyzed the monocyte and macrophage response to volumetric muscle loss injuries that result in fibrosis or regeneration and observed increased numbers of total immune cells, pro-inflammatory monocytes and macrophages, and scar-associated macrophages for VML injuries that result in fibrosis.

Vitamin A retinoic acid contributes to muscle stem cell and mitochondrial function loss in old age.

Adult stem cells decline in number and function in old age, and identifying factors that can delay or revert age-associated adult stem cell dysfunction are vital for maintaining a healthy lifespan. Here we show that vitamin A, a micronutrient that is derived from diet and metabolized into retinoic acid, acts as an antioxidant and transcriptional regulator in muscle stem cells. We first show that obstruction of dietary vitamin A in young animals drives mitochondrial and cell cycle dysfunction in muscle stem cells that mimics old age.

Skeletal muscle innervation: Reactive oxygen species as regulators of neuromuscular junction dynamics and motor unit remodeling.

This review explores the intricate processes of motor unit remodeling with a specific focus on the influence of reactive oxygen species (ROS) and oxidative stress on the primary cellular components: nerves/axons, muscle fibers, and muscle-resident glial cells. Emphasizing the role of redox biology, we highlight how oxidative stress impacts motor unit adaptation, injury response, and aging. By synthesizing findings from recent studies with seminal works, including investigations of myelin and terminal Schwann cells and neuromuscular junction (NMJ) dynamics, this review provides a comprehensive understanding of the molecular mechanisms underpinning motor unit maintenance and repair.

Decoding muscle-resident Schwann cell dynamics during neuromuscular junction remodeling.

This investigation leverages single-cell RNA sequencing (scRNA-Seq) to delineate the contributions of muscle-resident Schwann cells to neuromuscular junction (NMJ) remodeling by comparing a model of stable innervation with models of reinnervation following partial or complete denervation. The study discovered multiple distinct Schwann cell subtypes, including a novel terminal Schwann cell (tSC) subtype integral to the denervation-reinnervation cycle, identified by a transcriptomic signature indicative of cell migration and polarization. The data also characterizes three myelin Schwann cell subtypes, which are distinguished based on enrichment of genes associated with myelin production, mesenchymal differentiation or collagen synthesis.

Skeletal muscle structure, physiology, and function.

Contractions of skeletal muscles provide the stability and power for all body movements. Consequently, any impairment in skeletal muscle function results in some degree of instability or immobility. Factors that influence skeletal muscle structure and function are therefore of great interest scientifically and clinically.

Removal of Expressing Cells in Late Life has Moderate Beneficial Effects on Skeletal Muscle Function in Male Mice.

Aging results in the progressive accumulation of senescent cells in tissues that display loss of proliferative capacity and acquire a senescence-associated secretory phenotype (SASP). The tumor suppressor, p16 , which slows the progression of the cell cycle, is highly expressed in most senescent cells and the removal of p16-expressing cells has been shown to be beneficial to tissue health. Although much work has been done to assess the effects of cellular senescence on a variety of different organs, little is known about the effects on skeletal muscle and whether reducing cellular senescent load would provide a therapeutic benefit against age-related muscle functional decline.

Emerging molecular mediators and targets for age-related skeletal muscle atrophy.

The age-associated decline in muscle mass has become synonymous with physical frailty among the elderly due to its major contribution in reduced muscle function. Alterations in protein and redox homeostasis along with chronic inflammation, denervation, and hormonal dysregulation are all hallmarks of muscle wasting and lead to clinical sarcopenia in older adults. Reduction in skeletal muscle mass has been observed and reported in the scientific literature for nearly 2 centuries; however, identification and careful examination of molecular mediators of age-related muscle atrophy have only been possible for roughly 3 decades.