Anna Vainshtein, Bert Blaauw, Katrien De Bock, Pura Munoz-Canoves, Eric N Olson, Coen A C Ottenheijm, Erik A Richter, Jorge L Ruas, Laurent Schaffer, Bruce Spiegelman, Marco Sandri
Skeletal muscle is a central determinant of organismal health. Preserving muscle quality is therefore critical for preventing disease and sustaining quality of life across the lifespan. Despite its central role, the field lacks a unifying framework that defines the core properties of skeletal muscle health. Here, we propose a conceptual framework for muscle homeostasis built around seven interconnected hallmarks-metabolism and bioenergetics, proteostasis, genomics, excitability, structure, regeneration and cross-talk-that collectively govern muscle integrity, adaptability and resilience. Each hallmark is mechanistically grounded, quantifiable and potentially modifiable. This framework provides a unifying blueprint for the next generation of precision diagnostics and targeted therapies for preserving skeletal muscle health.