Age-related decline in a protein-cleaning process in muscles leads to worsening muscle disease

Declining chaperone-mediated autophagy was linked to skeletal muscle dysfunction, while boosting CMA partly improved ageing muscle phenotypes in mice.

This mechanistic study combined muscle-specific CMA-deficient mice, proteomic analyses, ageing and obesity contexts, old-mouse CMA upregulation, and confirmation of age-related CMA downregulation in human skeletal muscle.

Most functional and rescue evidence comes from mouse models, so the human data support age-related CMA decline but not clinical benefit from CMA upregulation.