临床及流行病学研究强烈提示睡眠呼吸暂停与老化及加速老化相关。SIRT1是关键的衰老相关基因，且调节与睡眠呼吸紊乱密切相关的5-HT系统，推测miR-34a -SIRT1-BNDF/IGF-1-5-HT/5-HT2R通路表达和功能下降可能是呼吸中枢老化或加速老化、功能下降进而产生睡眠呼吸紊乱的重要机制。通过分析老年鼠和成年鼠呼吸紊乱的差异及其与该通路表达的关系、间歇缺氧对大鼠呼吸紊乱的影响及其与该通路表达的关系、在体水平中枢干预该通路对呼吸暂停的影响、离体水平干预该通路对呼吸中枢神经核团电活动的影响、以及该通路在细胞的抗氧化应激过程中的作用等5个方面的研究，阐明miR-34a -SIRT1-BNDF/IGF-1-5-HT/5-HT2R通路在中枢老化或加速老化所致睡眠呼吸紊乱中的作用。从呼吸中枢老化的全新角度揭示OSASH本质，为正确认识其发病机制、寻找新药物靶点提供依据。

Brain aging is associated closely with sleep apnea and there exist accelerated aging in OSAHS patients. However, its molecular mechanisms is still unclear. As a critical anti-aging gene, SIRT1 might regulate the central 5-HT system, which has verified to play an important role in sleep apnea. Therefore, we make the following hypothesis that aging or oxidative stress could down-regulate the expression and function of miR-34a -SIRT1-BNDF/IGF-1-5-HT/5-HT2R signal pathway, which lead to the aging of respiratory center and more sleep apneas. This study includes the following aspects: The difference of aged and adult rats will be compared and intermittent hypoxia on sleep apnea will be tested; The role of miR-34a -SIRT1-BNDF/IGF-1-5-HT/5-HT2R pathway in the process of aging and intermittent hypoxia deteriorating sleep apnea will be tested in molecular level; Whether miR-34a -SIRT1-BNDF/IGF-1-5-HT/5-HT2R pathway plays a role in the anti-oxidative stress damage will be studied in cultured cell level; Whether regulating miR-34a -SIRT1-BNDF/IGF-1-5-HT/5-HT2R pathway can improve the activity of central respiratory neurons will be tested. Through the study as above, we could illustrate the role of miR-34a -SIRT1-BNDF/IGF-1-5-HT/5-HT2R in brain aging related sleep apnea. From the a new aspect, brain aging, to investigate the pathogenesis of sleep apnea will provide a new sight to recognize sleep apnea and possible Drug targets.