FoxO1 in skeletal muscle atrophy: Multifaceted regulatory mechanisms and therapeutic opportunities.

Abstract

Skeletal muscle, which accounts for nearly 40 % of total body mass, serves as the primary effector organ for locomotion, metabolism, and thermoregulation. Skeletal muscle atrophy, a common condition associated with aging, disease, and disability, significantly compromises patients' quality of life. This review focuses on the occurrence and progression of skeletal muscle atrophy. Forkhead box protein O1 (FoxO1) is a key regulatory factor that mediates pathological mechanisms through multidimensional molecular networks. It influences skeletal muscle metabolism via post-translational modifications (PTMs), dysregulated autophagy, an imbalanced inflammatory microenvironment, and the regulation of satellite cell function. Therapeutic strategies targeting FoxO1, such as resveratrol-induced SIRT1 activation and miR-486 mimics, have shown promising results in preclinical models. This review highlights the central role of FoxO1 in molecular pathways, proposes a potential framework for addressing muscle atrophy, and offers new insights into the treatment of sarcopenia and related diseases.