Tumour-induced dysregulation of cAMP–PKA–CREB1 signalling in skeletal muscle is shown to be a driver of mitochondrial dysfunction, contributing to cancer cachexia in mice.

In mdx mouse fetuses, the lack of dystrophin markedly impairs secondary myogenesis due to reduced muscle stem cell polarity. AAK1 deletion restores polarity and rescues secondary myogenesis, revealing...

The Advanced Cardiac Therapies Improving Outcomes Network formed a dystrophinopathy registry to define cardiac diagnostics, management, and advanced t…

Introduction: Head and neck cancer (HNC) accounts for ~4% of all cancers but causes ~15,000 deaths annually in the U.S. Over 40% of HNC patients present with cachexia, a severe comorbidity associated with skeletal muscle defects, worsened treatment response, and poor outcomes. The mechanisms behind HNC cachexia remain unclear, partly due to limited small animal models. This study characterizes functional and molecular features of cachexia in a novel preclinical model using tobacco-induced B0092 oral squamous cell carcinoma in C57BL/6J mice. Methods: C2C12 myotubes were exposed to various concentrations of B0092 conditioned media (CM) to assess effects on myotube diameter and expression of muscle-specific ubiquitin ligases (MuRF−1, Atrogin−1). C57BL/6J male and female mice were implanted with B0092 cells (5x105 cells) to investigate musculoskeletal effects of HNC. RNA sequencing of muscle identified gene signatures associated with cachexia. Results: Myotubes treated with B0092 CM showed atrophy already at 25% CM (−21%, p<0.01), along with elevated MuRF-1 (+81%, p<0.05) and Atrogin-1 (+27%, p<0.05). B0092 tumor growth in male mice led to muscle atrophy, reduced strength (−36%, p<0.001), and lower bone mineral density (−8%, p<0.01). Muscle atrophy correlated with increased MuRF-1 (+1.96-fold, p<0.05) and Atrogin-1 (+1.97-fold, p<0.05). Female mice exhibited moderate cachexia despite similar tumor size. RNA sequencing of muscle in male B0092 hosts revealed mitochondrial dysfunction and upregulation of proteasome- and translation-related pathways, supporting a shift toward protein degradation and impaired energy metabolism. Conclusion: These findings suggest that B0092-bearing mice are valuable to uncover novel molecular pathways and potential therapeutic targets for HNC cachexia.

Abstract. Muscle stem cells, or satellite cells, decline in number throughout the lifespan and may become senescent in very old age. Whether and how remain

Muscle stem cells rely on their niche for maintenance, yet how β-adrenergic innervation regulates these cells remains elusive. Here, we show that symp…

While low-dose adeno-associated virus (AAV) gene therapy has been generally well tolerated, multiple recent reports have documented fatalities associated with high-dose AAV vectors. These events have ...

Our findings suggest that blood Alzheimer’s disease-related biomarkers might help estimate progressive muscle strength decline among older adults, elucidating the influence of brain pathology and cogn...

Myogenic regulatory factors, including myoblast determination protein 1 (MyoD1 or MyoD) and myogenic factor 5 (Myf5), crucially regulate skeletal muscle lineage specification and development. Although...

During natural aging, skeletal muscle experiences impairments in mechanical performance due, in part, to changes in muscle architecture and size, notably with a loss of muscle cross-sectional area (CS...

Aims/hypothesis Disrupted energy balance is critical for the onset and development of type 2 diabetes mellitus. Understanding of the exact underlying metabolic mechanisms remains incomplete, but skele...

Cancer cachexia is a debilitating metabolic disorder characterized by involuntary loss of body and muscle mass, leading to increased morbidity and mor…

Abstract figure legend Common human and rodent muscle disuse models and associated changes in skeletal muscle mitochondrial function; respiration, redox stress and apoptotic cell death. I–V, complexe...

The effect of biological sex on rates of skeletal muscle mitochondrial respiration supported by creatine-dependent phosphate shuttling was previously unknown. The aim of this investigation was to tes...

The core circadian transcription factor BMAL1 regulates circadian-dependent myocardial injury.