Molecular Framework of the Onset and Progression of Skeletal Muscle Aging

TL;DR

This review explores how skeletal muscle begins to age, focusing on early molecular changes that occur before visible signs of aging appear.

Contribution

The paper highlights the importance of studying middle-aged muscle to understand the early onset of aging and identify potential biomarkers.

Findings

Middle-aged muscle shows early signs of metabolic and functional decline.

Linear and non-linear biomarkers are associated with the onset of skeletal muscle aging.

Early detection of these biomarkers could help develop interventions to delay aging-related decline.

Abstract

Aging is a multifactorial process that progressively disrupts cellular and tissue homeostasis, affecting all organ systems at distinct rates and predisposing individuals to chronic diseases such as cancer, type II diabetes, and sarcopenia. Among these systems, skeletal muscle plays a central role in healthspan decline, yet the precise onset of its deterioration remains unclear. Most studies emphasize late-life models, overlooking the transitional phase of middle age, when initial alterations emerge. Evidence indicates that middle-aged muscle exhibits aberrant metabolism, impaired insulin sensitivity, and an early, gradual reduction in mass, suggesting that decline begins long before overt sarcopenia. This narrative review synthesizes current findings on linear and non-linear molecular biomarkers associated with the onset of skeletal muscle aging, aiming to improve early detection of muscular alterations and support the development of interventions that delay or prevent functional decline.

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