低氧联合有氧/抗阻运动激活dme_circ_0001184/dme-miR-283-5p/dSir2信号通路的心脏增龄保护作用

circRNA增龄积累为衰老分子机理的研究提供了新的线索。dSir2是经典延寿核心因子，生物信息方法预测dme_circ_0001184、dme-miR-283-5p可能是dSir2的上游调控分子，前期在衰老心肌中检测到三者的高差异表达。心脏是低氧和运动应激反应最为敏感的器官，circRNA可被内外环境适宜刺激诱导。我们推测：低氧和运动是激活dme_circ_0001184/dme-miR-283-5p/dSir2通路抗心脏衰老的理想应激源。本项目拟应用离体实验证实三者的靶向结合，在此基础上，采用自主研发的新一代果蝇运动装置和低氧装置，建立有氧、抗阻、低氧联合运动果蝇模型，采用转基因和杂交技术构建dme_circ_0001184突变和过表达果蝇品系，研究三者的基因突变、功能拯救对老龄果蝇心脏表型的影响，明确低氧联合运动调控dSir2途径的上游事件，为心脏抗衰老的科学探索提供新的遗传学证据。

The accumulation of circRNA with aging provides a new clue for the study of the molecular mechanism of aging. dSir2 is the core factor of life extension. Bioinformatics method predicts that dme_circ_0001184 and dme-miR-283-5p may be the upstream regulatory molecules of dSir2. Previous studies have detected high differential expression of the three molecules in aging myocardium. The heart is the most sensitive organ to hypoxia and exercise stress, and circRNA can be induced by suitable stimulation of internal and external environment. We speculate that hypoxia and exercise are ideal stressors for activating dme_circ_0001184/dme-miR-283-5p/dSir2 pathway to play an anti-aging role. In this project, the targeting combination of the three was confirmed by in vitro experiments. On this basis, the aerobic, resistance and hypoxia combined exercise model of Drosophila melanogaster was established by using a new generation of self-developed Drosophila exercise device combined with hypoxia, and the dme_circ_0001184 mutation and overexpression Drosophila strains were constructed by transgenic and hybridization techniques to study the effects of gene mutation and functional rescue on the heart phenotype of aged Drosophila melanogaster. To identify the upstream events of dSir2 pathway regulated by hypoxia combined with exercise, and to provide new genetic evidence for the scientific exploration of cardiac anti-aging.