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

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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.