| Autor: |
Tezze C; Department of Biomedical Sciences, University of Padova, Padova, Italy.; Veneto Institute of Molecular Medicine, Padova, Italy., Amendolagine FI; Department of Biomedical Sciences, University of Padova, Padova, Italy.; Veneto Institute of Molecular Medicine, Padova, Italy., Nogara L; Department of Biomedical Sciences, University of Padova, Padova, Italy.; Veneto Institute of Molecular Medicine, Padova, Italy., Baraldo M; Department of Biomedical Sciences, University of Padova, Padova, Italy.; Veneto Institute of Molecular Medicine, Padova, Italy., Ciciliot S; Department of Biomedical Sciences, University of Padova, Padova, Italy.; Veneto Institute of Molecular Medicine, Padova, Italy., Arcidiacono D; Gastroenterology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy., Zaramella A; Gastroenterology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy., Masiero G; Department of Biomedical Sciences, University of Padova, Padova, Italy.; Veneto Institute of Molecular Medicine, Padova, Italy., Ferrarese G; Department of Biomedical Sciences, University of Padova, Padova, Italy.; Veneto Institute of Molecular Medicine, Padova, Italy., Realdon S; Oncological Gastroenterology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy., Blaauw B; Department of Biomedical Sciences, University of Padova, Padova, Italy.; Veneto Institute of Molecular Medicine, Padova, Italy., Detienne G; Rejuvenate Biomed, Diepenbeek, Belgium., Beliën AT; Rejuvenate Biomed, Diepenbeek, Belgium., Sandri M; Department of Biomedical Sciences, University of Padova, Padova, Italy.; Veneto Institute of Molecular Medicine, Padova, Italy.; Department of Medicine, McGill University, Montreal, Quebec, Canada., Mercken EM; Rejuvenate Biomed, Diepenbeek, Belgium. |
| Abstrakt: |
Age-associated sarcopenia, characterized by a progressive loss in muscle mass and strength, is the largest cause of frailty and disability in the elderly worldwide. Current treatments involve nonpharmacological guidelines that few subjects can abide by, highlighting the need for effective drugs. Preclinical models were employed to test the benefits of RJx-01, a combination drug composed of metformin and galantamine, on sarcopenia. In worms, RJx-01 treatment improved lifespan, locomotion, pharyngeal pumping, and muscle fiber organization. The synergistic effects of RJx-01 were recapitulated in a transgenic mouse model that displays an exacerbated aging phenotype (Opa1-/-). In these mice, RJx-01 ameliorated physical performance, muscle mass and force, neuromuscular junction stability, and systemic inflammation. RJx-01 also improved physical performance and muscle strength in 22-month-old WT mice and also improved skeletal muscle ultrastructure, mitochondrial morphology, autophagy, lysosomal function, and satellite cell content. Denervation and myofiber damage were decreased in RJx-01-treated animals compared with controls. RJx-01 improved muscle quality rather than quantity, indicating that the improvement in quality underlies the beneficial effects of the combination drug. The studies herein indicate synergistic beneficial effects of RJx-01 in the treatment of sarcopenia and support the pursuit of RJx-01 in a human clinical trial as a therapeutic intervention for sarcopenia. |
