Muscle weakness and atrophy are associated with decreased regenerative capacity and changes in mTOR signaling in skeletal muscles of venerable (18-24-month-old) dystrophic mdx mice

• Published in: Muscle & nerve Vol. 41; no. 6; pp. 809 - 818
• Main Authors: Mouisel, E., Vignaud, A., Hourdé, C., Butler-Browne, G., Ferry, A.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-06-2010; Wiley
• Subjects: aging; Aging - physiology; Animals; Biological and medical sciences; Diseases of striated muscles. Neuromuscular diseases; force production; Fundamental and applied biological sciences. Psychology; Medical sciences; Mice; Mice, Inbred mdx; Muscle Fatigue - physiology; Muscle Proteins - metabolism; Muscle Weakness - pathology; Muscle Weakness - physiopathology; Muscle, Skeletal - pathology; Muscle, Skeletal - physiology; Muscle, Skeletal - physiopathology; Muscular Dystrophy, Animal - physiopathology; Muscular Dystrophy, Duchenne - physiopathology; Nerve Regeneration; Neurology; Phosphatidylinositol 3-Kinases - metabolism; Reference Values; Regeneration; Signal Transduction - physiology; Stress, Mechanical; Striated muscle. Tendons; Vertebrates: osteoarticular system, musculoskeletal system; Phosphorylation; Enzyme; Amyotrophy; Force; Transferases; Non-specific serine/threonine protein kinase; Rodentia; Striated muscle; Muscle contraction; Recovery; Regeneration; Signal transduction; Striated muscle disease; Vertebrata; Mammalia; Mouse; force production; Weakness; Dystrophy; aging
• ISSN: 0148-639X; 1097-4598
• DOI: 10.1002/mus.21624

The muscles of mdx mice progressively deteriorate with age. We wanted to know whether this is associated with a decrease in regenerative capacity and/or changes in the mammalian target of rapamycin complex (mTOR) signaling pathway. Muscles of mdx mice aged 5 weeks, 5, 12, and 18–24 months were studied. Maximal force and muscle weight of the older mice were decreased as compared to younger adult mice. Activation of the mTOR signaling pathway, i.e., phosphorylation of Akt (also known as protein kinase B) and ribosomal protein S6 was also reduced in the older mice. Moreover, 14 days after cardiotoxin injury the degree of recovery of maximal force and muscle weight were less in the older mice. In contrast to younger mice, there was also activation of the mTOR pathway during regeneration in the older mice. Progressive muscle weakness and atrophy in mdx mouse muscle is associated with a decline in regenerative potential and changes in activation of the mTOR signaling pathway. Muscle Nerve 000: 000–000, 2010