人口老龄化是我国面临的一个非常严峻的社会问题。探讨衰老所致的血压稳态失衡的发生机制，寻找有效防治措施尤为必要。本项目通过检测不同年龄健康受试者压力感受性反射敏感性与血浆TMAO水平的相关性，并在衰老大鼠上明确压力感受性反射钝化及血压稳态失衡与TMAO水平增高有关。应用脑片膜片钳、细胞培养、分子生物学技术等，明确TMAO含量增高诱发SIRT1活性下降进而引起RVLM区神经元细胞衰老及衰老细胞分泌表型转化可能参与了衰老大鼠RVLM区的中枢炎症反应，从而导致交感神经过度激活，压力感受性反射钝化，引起血压稳态失衡；H2S可能通过提高神经元SIRT1活性减低中枢炎症，敏化衰老大鼠压力感受性反射，维持血压稳态。应用微量热泳动仪、Biacore、XAFS等多种光谱学方法探讨H2S是否与SIRT1活性中心的锌离子结合来直接提高其活性，从而揭示衰老所致血压稳态失衡发生的神经和分子机制，为其防治提供理论依据。

Aging of population is a grim social problem in our country. Therefore, it is particularly necessary to investigate the molecular mechanism that leads to the disrupted homeostasis of blood pressure caused by aging and explore the effective prevention and therapy strategies. With this in mind, baroreflex sensitivity and plasma TMAO levels in healthy subjects of different ages is determined to investigate the correlation between them. And then, the aged rat is used to confirm that decreased baroreflex sensitivity and disrupted blood pressure homeostasis are associated with increased TMAO levels. Patch clamp, cell culture, molecular biology techniques, etc. are used to clear that the increased TMAO levels induce the decrease of SIRT1 activity, which promotes senescence and initiates senescence-associated secretory shenotype (SASP) of neuronal cells in RVLM and the senescent cells may be involved in the central inflammation of RVLM in the aged rats，which leads to excessive activation of sympathetic nerves, decrease baroreflex sensitivity and disrupt blood pressure homeostasis. However，H2S may reduce central inflammation by increasing neuronal SIRT1 activity, then increase baroreflex sensitivity and maintain blood pressure homeostasis in the aged rats. Microscale thermophoresis, Biacore, XAFS and other spectroscopy methods are used to explore whether H2S binds directly to the zinc ion of the SIRT1 active center to directly increase its activity. This will shed light on the neurological and molecular mechanisms of disrupted blood pressure homeostasis caused by aging and provide theoretical bases for its prevention and therapy.