Induction of ACE2 expression in skeletal muscles in aged mice by transcutaneous electrical stimulation

血管紧张素II（Angiotensin II，Ang II）在衰老及衰老相关疾病中起着重要作用。 抑制血管紧张素II的生产和活动已显示出各种抗衰老作用。昂二是 由血管紧张素转化酶（ACE）从Ang I产生。最近的研究表明 ACE 2是ACE的同源物，可通过将Ang I转化为Ang 1-9来减少Ang II的产生， 并将Ang II转化为Ang 1-7。除了心脏肾脏血管内皮细胞 与平滑肌细胞相比，ACE 2也在骨骼肌中表达。我们的初步数据 显示在衰老小鼠的骨骼肌中ACE 2蛋白水平显著降低， 而经皮电神经刺激（TENS）坐骨神经增加ACE 2 在骨骼肌中的表达。我们假设刺激骨骼肌 ACE 2在骨骼肌中的表达，并降低血浆Ang II水平和增加Ang 1-7， 老老鼠为了验证这一假设，这项研究将首先测试TENS-是否增加肌肉 ACE 2在老年小鼠中的表达是刺激和收缩依赖的; 确定TENS增强的ACE 2表达是否导致血浆Ang 1-7增加， 降低老龄小鼠的Ang Ⅱ水平。这项研究的结果将为我们的未来奠定基础 研究通过增强内源性抗血管紧张素来探索和开发新的抗衰老方法 II机制，如诱导骨骼肌中ACE 2表达，具有非侵入性，非侵入性， 化学方法，如TENS。

Angiotensin II (Ang II) plays a detrimental role in aging and aging related diseases. Inhibitions of Ang II production and activities have shown various anti-aging effects. Ang II is produced from Ang I by angiotensin converting enzyme (ACE). Recent studies have revealed that ACE2, a homologue of ACE, can reduce Ang II production by converting Ang I into Ang 1-9 and converting Ang II into Ang 1-7. In addition to the heart, kidneys, vascular endothelial cells and smooth muscle cells, ACE2 also expresses in skeletal muscles. Our preliminary data showed that ACE2 protein level was significantly reduced in skeletal muscles in ageing mice, whereas transcutaneous electrical nerve stimulation (TENS) of sciatic nerve increased ACE2 expression in skeletal muscles. We hypothesize that stimulation of skeletal muscles increases ACE2 expression in skeletal muscles and reduce plasma Ang II level and increase Ang 1-7 in aged mice. To test this hypothesis, this study will first test whether TENS- increase muscle ACE2 expression is stimulation and contraction dependent in aged mice; Then we will determine whether TENS-enhanced ACE2 expression causes increased plasma Ang 1-7 and decreasd Ang II in aged mice. The results of this study will build a foundation for our future study to explore and develop novel anti-ageing approaches by enhancing endogenous anti-Ang II mechanisms, such as inducing ACE2 expression in skeletal muscles, with non-invasive, non- chemical means, such as TENS.