The hallmarks of skeletal muscle health

Abstract

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. This Review defines seven hallmarks of skeletal muscle homeostasis, providing a unifying framework for understanding, measuring and preserving muscle health.