高强度间歇训练（HIIT）可防治衰老性肌萎缩，但机制不清。前期研究发现，HIIT激活AKT/FoxO1通路，改善衰老骨骼肌自噬/线粒体/氧化应激/凋亡途径；文献报道miR-486通过抑制PTEN表达激活AKT/FoxO1通路，而运动能通过阻断外泌体介导的miR-486输出调控骨骼肌miR-486水平。我们预实验发现HIIT上调衰老骨骼肌miR-486、FoxO1并抑制PTEN mRNA表达。推测HIIT调控PTEN/AKT/FoxO1通路与阻断衰老骨骼肌外泌体介导的miR-486输出有关。基于前期研究，拟对增龄大鼠骨骼肌注射miRNA-486激动剂和拮抗剂的腺相关病毒和外泌体抑制剂，通过外泌体分离、蛋白质印迹、免疫荧光、RT-PCR等技术，论证阻断骨骼肌外泌体miR-486输出介导HIIT保护效应；以体外肌细胞与外泌体融合明确其下游机制。本研究将为HIIT干预衰老性肌萎缩提供新的理论依据。

High-intensity interval training (HIIT) is currently considered the primary countermeasure to sarcopenia, the underlying molecular mechanisms are not well understood. We have previously found that HIIT activated the AKT/FoxO1 signaling pathway may be associated with improvements in autophagy/oxidative stress/mitochondrial function/apoptosis. The previous study confirmed that miR-486 activated the AKT/FoxO1 pathway meditated by the downregulation of PTEN expression in skeletal muscle, and exercise training upregulated miR-486 level by inhibiting exosome-mediated miR-486 export. Additionally, HIIT increased miR-486 and FoxO1 mRNA levels, but reduced PTEN mRNA in aged skeletal muscle. It may thus be speculated that HIIT regulate PTEN/AKT/FoxO1 pathway may be through inhibiting exosome-mediated miR-486 export. The present study is designed to confirming benefits impact of miR-486 and downregulation of exosome-mediated miR-486 export plays a pivotal positive role in mediating HIIT preventing sarcopenia by injection of an adeno-associated virus encoding the miRNA-486 agomir and antagomir, exosome secretion inhibitor GW4869 into the gastrocnemius muscle of aged rats. Culture L6 muscle cells in vitro, and incubated with exosomes were isolated from conditioned media of gastrocnemius muscle in both control and HIIT groups rats, to investigate the effect of exosome-mediated miR-486 act via downstream. This research project will provide new information and potential therapeutic target about long-term HIIT protocol prevents sarcopenia.