Comparative Analyses of mTOR/Akt and Muscle Atrophy-Related Signaling in Aged Respiratory and Gastrocnemius Muscles

• Published in: International journal of molecular sciences Vol. 21; no. 8; p. 2862
• Main Authors: Kim, Kun Woo, Cho, Hye-Jeong, Khaliq, Sana Abdul, Son, Kuk Hui, Yoon, Mee-Sup
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20.04.2020; MDPI
• Subjects: Age; Aging; Aging - metabolism; AKT protein; Animals; Atrophy; Autophagy; Autophagy - genetics; Biomarkers; Chronic obstructive pulmonary disease; Diaphragm; Diaphragms; Disease Models, Animal; Forkhead protein; FOXO1 protein; gastrocnemii; Gene Expression; Homeostasis; intercostal muscles; Intercostal Muscles - metabolism; Kinases; Mammals; Metabolism; Mitochondria; Mitochondria, Muscle - genetics; Mitochondria, Muscle - metabolism; muscle atrophy; Muscle function; Muscle, Skeletal - metabolism; Muscles; Muscular Atrophy - genetics; Muscular Atrophy - metabolism; Muscular Atrophy - pathology; Phagocytosis; Phosphorylation; Proteasomes; Protein synthesis; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Quality control; Rats; Respiratory Muscles - metabolism; Sarcopenia; Signal Transduction; Skeletal muscle; TOR protein; TOR Serine-Threonine Kinases - metabolism; Transcription factors; Ubiquitin; Ubiquitin - genetics; Ubiquitin - metabolism; diaphragm; autophagy; gastrocnemii; muscle atrophy; intercostal muscles; sarcopenia
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21082862

Sarcopenia is the degenerative loss of skeletal muscle mass and function associated with aging and occurs in the absence of any underlying disease or condition. A comparison of the age-related molecular signaling signatures of different muscles has not previously been reported. In this study, we compared the age-related molecular signaling signatures of the intercostal muscles, the diaphragm, and the gastrocnemii using 6-month and 20-month-old rats. The phosphorylation of Akt, ribosomal S6, and Forkhead box protein O1 (FoxO1) in diaphragms significantly increased with age, but remained unchanged in the intercostal and gastrocnemius muscles. In addition, ubiquitin-proteasome degradation, characterized by the levels of MuRF1 and Atrogin-1, did not change with age in all rat muscles. Interestingly, an increase in LC3BII and p62 levels marked substantial blockage of autophagy in aged gastrocnemii but not in aged respiratory muscles. These changes in LC3BII and p62 levels were also associated with a decrease in markers of mitochondrial quality control. Therefore, our results suggest that the age-related signaling events in respiratory muscles differ from those in the gastrocnemii, most likely to preserve the vital functions played by the respiratory muscles.