Tetramethylpyrazine Nitrone alleviates D-galactose-induced murine skeletal muscle aging and motor deficits by activating the AMPK signaling pathway - 22/03/24
Abstract |
Tetramethylpyrazine nitrone (TBN), a novel derivative of tetramethylpyrazine (TMP) designed and synthesized by our group, possesses multi-functional mechanisms of action and displays broad protective effects in vitro and in animal models of age-related brain disorders such as stroke, Alzheimer’s disease (AD), Amyotrophic Lateral Sclerosis (ALS) and Parkinson’s disease (PD). In the present report, we investigated the effects of TBN on aging, specifically on muscle aging and the associated decline of motor functions. Using a D-galactose-induced aging mouse model, we found that TBN could reverse the levels of several senescence and aging markers including p16, p21, ceramides, and telomere length and increase the wet-weight ratio of gastrocnemius muscle tissue, demonstrating its efficacy in ameliorating muscle aging. Additionally, the pharmacological effects of TBN on motor deficits (gait analysis, pole-climbing test and grip strength test), muscle fibrosis (hematoxylin & eosin (HE), Masson staining, and αSMA staining), inflammatory response (IL-1β, IL-6, and TNF-α), and mitochondrial function (ATP, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were also confirmed in the D-galactose-induced aging models. Further experiments demonstrated that TBN alleviated muscle aging and improved the decline of age-related motor deficits through an AMPK-dependent mechanism. These findings highlight the significance of TBN as a potential anti-aging agent to combat the occurrence and development of aging and age-related diseases.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Schematic diagram illustrating the protective effect of TBN treatment on muscle aging and age-related motor deficits in D-galactose-induced mouse aging model. TBN activated the AMPK signaling pathway, which finally restored mitochondrial integrity, suppressed NF-κB-Murf1/Atrogin-1-mediated muscle protein degradation, thereby improving the decline of age-related motor deficits.
Schematic diagram illustrating the protective effect of TBN treatment on muscle aging and age-related motor deficits in D-galactose-induced mouse aging model. TBN activated the AMPK signaling pathway, which finally restored mitochondrial integrity, suppressed NF-κB-Murf1/Atrogin-1-mediated muscle protein degradation, thereby improving the decline of age-related motor deficits.Le texte complet de cet article est disponible en PDF.
Highlights |
• | TBN ameliorates D-galactose-induced muscle aging and improves age-related motor deficits in mice |
• | TBN reduces aged-related muscular fibrosis and atrophy, and inflammatory response |
• | TBN improves age-related mitochondrial impairment and activated the AMPK signaling pathway |
• | TBN suppresses muscle atrophy by modulating NF-κB-Murf1/Atrogin-1 signaling |
• | TBN mitigates muscle aging and age-related motor deficits via AMPK signaling activation |
Keywords : Tetramethylpyrazine nitrone (TBN), Muscle aging, Motor deficits, Mitochondrial function, AMPK signaling
Plan
Vol 173
Article 116415- avril 2024 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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