Age-related decline of chaperone-mediated autophagy in skeletal muscle leads to progressive myopathy.

ABSTRACT: Chaperone-mediated autophagy (CMA) contributes to proteostasis maintenance by selectively degrading a subset of proteins in lysosomes. CMA declines with age in most tissues, including skeletal muscle. However, the role of CMA in skeletal muscle and the consequences of its decline remain poorly understood. Here we demonstrate that CMA regulates skeletal muscle function. We show that CMA is upregulated in skeletal muscle in response to starvation, exercise and tissue repair, but declines in ageing and obesity. Using a muscle-specific CMA-deficient mouse model, we show that CMA loss leads to progressive myopathy, including reduced muscle force and degenerative myofibre features. Comparative proteomic analyses reveal CMA-dependent changes in the mitochondrial proteome and identify the sarcopla

SUBMITTER: Santiago-Fernandez O 

PROVIDER: S-EPMC12727505 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature