Extracellular matrix dysfunction promotes mitochondrial defects and ectopic adipocyte infiltration in skeletal muscle

Einleitung Aging is associated with a progressive decline of skeletal muscle function. In older age, adipocytes accumulate between skeletal muscle fibers and may promote loss of muscle strength and muscular atrophy. Extracellular matrix (ECM) components are extrinsic factors of the stem cell niche necessary to maintain muscle regeneration and metabolic function. Here, we hypothesize that the ECM-components secreted by muscle-resident fibro-adipogenic progenitor cells (FAPs), might play a major role in the age-associated muscle disorders that contribute to decreased muscle function.

Methoden Microarray analysis of aged FAPs was used to identify matrix components and cell culture and mouse models with inactivation of this matricellular proteins were analyzed.

Ergebnisse Aging resulted in a concerted down-regulation of ECM genes. Moreover, metabolic analysis of aged and loss-of-function mice models showed a reduction in mitochondrial function in muscle tissue. Moreover, dysregulation of the ECM resulted in a reduction of muscle strength, metabolic flexibility, and muscle regeneration. In addition, FAPs from aged and ECM-impaired mice showed increased adipogenesis.

Schlussfolgerung These results indicate that alterations in the ECM might be associated with the fibro-adipogenic switch observed in aged muscle. Therefore, the ECM might serve as potential therapeutic target to preserve healthy muscle metabolism in the elderly.

Publication History

Article published online:
04 September 2020