Energy Sensing Networks and Skeletal Muscle Plasticity in Health and Disease

Skeletal muscle is a remarkably plastic tissue that continually adapts to changes in energetic demand, nutrient availability, mechanical loading, and physiological stress. These adaptive responses are orchestrated by interconnected energy sensing networks that regulate metabolism, protein turnover, mitochondrial function, regeneration, inter organ communication, neural input and overall tissue remodeling. Through the integration of biochemical and mechanical cues, these signalling pathways coordinate skeletal muscle plasticity across development, exercise, aging, injury, and disease while playing a central role in whole body metabolic homeostasis.

While the AMPK–mTOR–SIRT–PGC-1α axis remains a cornerstone of skeletal muscle energy sensing, recent discoveries have expanded this framework to encompass nutrient, calcium, redox, hypoxia, inflammatory, circadian, and mechanosensitive signalling pathways that collectively shape muscle phenotype and function. Advances in genomics, proteomics, metabolomics, spatial biology, and systems level analyses have further revealed extensive crosstalk between these pathways, highlighting the complexity of the molecular networks that govern muscle adaptation. Understanding how these signalling networks interact across physiological and pathological contexts is a major challenge and presents an important opportunity for developing therapies that preserve or restore muscle health.

This Research Topic aims to provide a platform for studies investigating the molecular and physiological mechanisms through which energy sensing networks regulate skeletal muscle plasticity in health and disease. We welcome original research, reviews, perspectives, and methodological articles spanning basic, translational, and clinical science. Topics of interest include, but are not limited to, exercise adaptation and training responses; mitochondrial biology and bioenergetics; nutrient sensing and metabolic flexibility; protein synthesis, degradation, autophagy, and proteostasis; muscle stem cells, regeneration, and repair; mechanotransduction; myokines and inter organ communication; aging and sarcopenia; cachexia and disuse atrophy; obesity and metabolic disease; inherited and acquired neuromuscular and neurodegenerative disorders; and pharmacological, nutritional, genetic, or exercise based interventions targeting these pathways.

We also encourage submissions employing emerging technologies, including single cell and spatial omics, multiomics integration, advanced microscopy imaging, computational biology, and systems physiology, to uncover novel regulators of skeletal muscle adaptation and identify new therapeutic opportunities.

By bringing together diverse perspectives across molecular, cellular, physiological, and clinical disciplines, this Research Topic aims to provide a comprehensive overview of the signalling networks that coordinate skeletal muscle plasticity. Ultimately, we hope this collection will stimulate interdisciplinary collaboration, highlight emerging concepts, and accelerate the translation of fundamental discoveries into strategies that preserve muscle function, enhance metabolic health, and improve outcomes across the lifespan.

Guest Editor Dr. David M. Thomson has received sponsored research funding from Biolexis Therapeutics on work related to AMPK and GLP-1 agonists, and continues to consult for them.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Conceptual Analysis
• Data Report
• Editorial
• FAIR² Data
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Conceptual Analysis
• Data Report
• Editorial
• FAIR² Data
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Skeletal muscle plasticity, Energy sensing, AMPK/mTOR/SIRT/PGC-1α, Mitochondrial bioenergetics, Muscle regeneration, Sarcopenia, Cachexia, Metabolic flexibility

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.