Combined exercise-induced modulation of Notch pathway and muscle quality in senescence-accelerated mice

• Published in: Pflügers Archiv Vol. 477; no. 3; pp. 393 - 405
• Main Authors: Pinto, Ana P., Sarni, Ângelo Augusto J., Tavares, Maria Eduarda A., da Rocha, Alisson L., Carolino, Ruither O. Gomes, de Sousa Neto, Ivo V., Da Silva Ferreira, Driele C., Munoz, Vitor R., Teixeira, Giovana R., Simabuco, Fernando M., Pauli, José R., Cintra, Dennys E., Ropelle, Eduardo R., de Freitas, Ellen C., da Silva, Adelino S. R.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2025; Springer Nature B.V
• Subjects: Aging - metabolism; Aging - physiology; Animals; Autophagy; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell Line; Exercise; Human Physiology; Humans; Immunoblotting; Interleukin 10; Interleukin-10 - genetics; Interleukin-10 - metabolism; Male; Mice; Molecular Medicine; Muscle, Skeletal - metabolism; Muscle, Skeletal - physiology; Musculoskeletal system; Myoblasts; Myoblasts - metabolism; Neurosciences; Physical activity; Physical Conditioning, Animal - physiology; Physical fitness; Physiology; Quadriceps muscle; Receptor, Notch2 - genetics; Receptor, Notch2 - metabolism; Receptors; Receptors, Notch - metabolism; Reverse transcription; Senescence; Signal transduction; Signal Transduction - physiology; Skeletal muscle; Transcription Factor HES-1 - genetics; Transcription Factor HES-1 - metabolism; Physical exercise; Aging; Muscle development; Molecular pathway
• ISSN: 0031-6768; 1432-2013; 1432-2013
• DOI: 10.1007/s00424-024-03048-2

The Notch signaling pathway is crucial for skeletal muscle development, regeneration, inflammation, and aging. This study investigated the association between interleukin-10 (IL-10) and the Notch pathway in C2C12 cells, as well as explored the effects of combined endurance and resistance exercise on the Notch and autophagy pathways in the skeletal muscle of senescence-accelerated mouse-resistant 1 Sedentary (SAMR1 CT), SAMR1 exercised (SAMR1 EX), senescence-accelerated prone mouse 8 Sedentary (SAMP8 CT), and SAMP8 exercised (SAMP8 EX). C2C12 myoblasts were transfected with siIL-10. Histological analysis, reverse transcription-quantitative polymerase chain reaction, and immunoblotting were performed on the quadriceps and tibialis anterior muscles. A publicly available dataset was analyzed to assess the Notch pathway in older men. In summary, IL-10 knockdown in myoblasts reduced the Notch pathway gene and protein expression. In SAMP8 mice, combined exercise improved muscle fiber organization, enhanced balance and coordination, and increased Notch2 and Hes1 mRNA levels. NOTCH2 mRNA levels were also higher in older men compared to young subjects with similar physical activity levels. These findings suggest that combined physical exercise enhances muscle regeneration via the Notch pathway in aged muscle.