RRC ID 80105
Author Noguchi I, Maeda H, Kobayashi K, Nagasaki T, Kato H, Yanagisawa H, Wada N, Kanazawa G, Kaji T, Sakai H, Fujimaki S, Ono Y, Taguchi K, Chuang VTG, Saruwatari J, Otagiri M, Watanabe H, Maruyama T.
Title Carbon monoxide-loaded cell therapy as an exercise mimetic for sarcopenia treatment.
Journal Free Radic Biol Med
Abstract Sarcopenia is characterized by loss of muscle strength and muscle mass with aging. The growing number of sarcopenia patients as a result of the aging population has no viable treatment. Exercise maintains muscle strength and mass by increasing peroxisome growth factor activating receptor γ-conjugating factor-1α (PGC-1α) and Akt signaling in skeletal muscle. The present study focused on the carbon monoxide (CO), endogenous activator of PGC-1α and Akt, and investigated the therapeutic potential of CO-loaded red blood cells (CO-RBCs), which is bioinspired from in vivo CO delivery system, as an exercise mimetic for the treatment of sarcopenia. Treatment of C2C12 myoblasts with the CO-donor increased the protein levels of PGC-1α which enhanced mitochondrial biogenesis and energy production. The CO-donor treatment also activated Akt, indicating that CO promotes muscle synthesis. CO levels were significantly elevated in the skeletal muscle of normal mice after intravenous administration of CO-RBCs. Furthermore, CO-RBCs restored the mRNA expression levels of PGC-1α in the skeletal muscle of two experimental sarcopenia mouse models, denervated (Den) and hindlimb unloading (HU) models. CO-RBCs also restored muscle mass in Den mice by activating Akt signaling and suppressing the muscle atrophy factors myostatin and atrogin-1, and oxidative stress. Treadmill tests further showed that the reduced running distance in HU mice was significantly restored by CO-RBC administration. These findings suggest that CO-RBCs have potential as an exercise mimetic for sarcopenia treatment.
Volume 220
Pages 67-77
Published 2024-8-1
DOI 10.1016/j.freeradbiomed.2024.04.231
PII S0891-5849(24)00410-6
PMID 38657755
MeSH Animals Carbon Monoxide* / metabolism Carbon Monoxide* / pharmacology Cell Line Cell- and Tissue-Based Therapy / methods Disease Models, Animal Humans Male Mice Mice, Inbred C57BL Muscle Proteins / genetics Muscle Proteins / metabolism Muscle, Skeletal* / drug effects Muscle, Skeletal* / metabolism Muscle, Skeletal* / pathology Myoblasts / drug effects Myoblasts / metabolism Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha* / genetics Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha* / metabolism Physical Conditioning, Animal Proto-Oncogene Proteins c-akt / metabolism Sarcopenia* / drug therapy Sarcopenia* / metabolism Sarcopenia* / pathology Sarcopenia* / therapy Signal Transduction / drug effects
Resource
Human and Animal Cells C2C12(RCB0987)