State Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, Frontiers Science Center for Animal Breeding and Sustainable Production, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
Institute of Animal Husbandry and Veterinary Sciences, Hubei Academy of Agricultural Sciences, Wuhan 430064, China.
Sci Adv. 2024 Sep 20;10(38):eadj4122. doi: 10.1126/sciadv.adj4122.
Sarcopenia is characterized by accelerated muscle mass and function loss, which burdens and challenges public health worldwide. Several studies indicated that selenium deficiency is associated with sarcopenia; however, the specific mechanism remains unclear. Here, we demonstrated that selenoprotein W (SELENOW) containing selenium in the form of selenocysteine functioned in sarcopenia. SELENOW expression is up-regulated in dexamethasone (DEX)-induced muscle atrophy and age-related sarcopenia mouse models. Knockout (KO) of SELENOW profoundly aggravated the process of muscle mass loss in the two mouse models. Mechanistically, KO suppressed the RAC1-mTOR cascade by the interaction between SELENOW and RAC1 and induced the imbalance of protein synthesis and degradation. Consistently, overexpression of SELENOW in vivo and in vitro alleviated the muscle and myotube atrophy induced by DEX. SELENOW played a role in age-related sarcopenia and regulated the genes associated with aging. Together, our study uncovered the function of SELENOW in age-related sarcopenia and provides promising evidence for the prevention and treatment of sarcopenia.
肌肉减少症的特征是肌肉质量和功能加速丧失，给全球公共卫生带来了负担和挑战。有几项研究表明，硒缺乏与肌肉减少症有关；然而，具体机制尚不清楚。在这里，我们证明了含有硒代半胱氨酸形式硒的硒蛋白 W（SELENOW）在肌肉减少症中发挥作用。SELENOW 的表达在地塞米松（DEX）诱导的肌肉萎缩和与年龄相关的肌肉减少症小鼠模型中上调。SELENOW 的敲除（KO）在两种小鼠模型中显著加剧了肌肉质量损失的过程。在机制上，SELENOW 通过与 RAC1 的相互作用抑制了 RAC1-mTOR 级联反应，导致蛋白质合成和降解失衡。一致地，体内和体外过表达 SELENOW 减轻了 DEX 诱导的肌肉和肌管萎缩。SELENOW 在与年龄相关的肌肉减少症中发挥作用，并调节与衰老相关的基因。总之，我们的研究揭示了 SELENOW 在与年龄相关的肌肉减少症中的作用，并为肌肉减少症的预防和治疗提供了有希望的证据。
