Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu 42988, Republic of Korea.
CTCELLS, Inc., Daegu 42988, Republic of Korea.
Proc Natl Acad Sci U S A. 2023 Aug 15;120(33):e2300036120. doi: 10.1073/pnas.2300036120. Epub 2023 Aug 7.
While the world is rapidly transforming into a superaging society, pharmaceutical approaches to treat sarcopenia have hitherto not been successful due to their insufficient efficacy and failure to specifically target skeletal muscle cells (skMCs). Although electrical stimulation (ES) is emerging as an alternative intervention, its efficacy toward treating sarcopenia remains unexplored. In this study, we demonstrate a silver electroceutical technology with the potential to treat sarcopenia. First, we developed a high-throughput ES screening platform that can simultaneously stimulate 15 independent conditions, while utilizing only a small number of human-derived primary aged/young skMCs (hAskMC/hYskMC). The in vitro screening showed that specific ES conditions induced hypertrophy and rejuvenation in hAskMCs, and the optimal ES frequency in hAskMCs was different from that in hYskMCs. When applied to aged mice in vivo, specific ES conditions improved the prevalence and thickness of Type IIA fibers, along with biomechanical attributes, toward a younger skMC phenotype. This study is expected to pave the way toward an electroceutical treatment for sarcopenia with minimal side effects and help realize personalized bioelectronic medicine.
随着世界迅速向超老龄化社会转变,由于药物治疗的疗效不足且不能特异性靶向骨骼肌细胞(skMCs),迄今为止,针对肌少症的药物治疗方法尚未取得成功。尽管电刺激(ES)作为一种替代干预手段正在出现,但它对肌少症的疗效仍有待探索。在本研究中,我们展示了一种具有治疗肌少症潜力的银电疗技术。首先,我们开发了一种高通量的 ES 筛选平台,该平台可以同时刺激 15 种独立条件,同时仅使用少量人源原代老年/年轻 skMC(hAskMC/hYskMC)。体外筛选表明,特定的 ES 条件诱导 hAskMC 发生肥大和年轻化,并且 hAskMC 中的最佳 ES 频率与 hYskMC 中的不同。当应用于体内老年小鼠时,特定的 ES 条件改善了 IIA 型纤维的发生率和厚度,以及生物力学特性,使其向更年轻的 skMC 表型发展。本研究有望为肌少症的电疗治疗铺平道路,其副作用最小,并有助于实现个性化的生物电子医学。