Synergistic Electroceutical-Glucocorticoid Intervention Mitigates Dexamethasone-Induced Muscle Atrophy in Aging Skeletal Muscle

Abstract Dexamethasone (DEX), a synthetic glucocorticoid widely prescribed for allergic and inflammatory diseases, is known to induce adverse effects, particularly skeletal muscle atrophy. DEX-induced atrophy exacerbates sarcopenia and has a more pronounced impact on aged skeletal muscle than on young skeletal muscle. To address this unmet clinical need, we introduce an electroceutical approach that counteracts DEX-induced muscle atrophy and enhances functional recovery in aging muscle. When applied to both young and aged human-derived skeletal muscle cells (skMCs) exhibiting DEX-induced atrophy, electroceutical treatment promoted recovery of myotube diameter and upregulated hypertrophy-related gene expression. Furthermore, in a preclinical study, young and aged mice treated with DEX to induce muscle atrophy exhibited significant muscle recovery following electroceutical treatment. This effect was evident from the restored cross-sectional area (CSA) of type IIA muscle fibers and the upregulation of hypertrophy-related genes. This study highlights electroceuticals as a pioneering non-pharmacological strategy complementary to glucocorticoid therapies, potentially transforming clinical outcomes and quality of life, particularly for older populations vulnerable to muscle wasting.