随着人口老龄化进程的加快，脑衰老相关疾病的发病率逐年升高，其机制未明。研究显示老年脑内淋巴系统功能下降可能加速了脑衰老进程，并与脑衰老相关疾病的发生发展密切相关。我们前期发现Omega-3 PUFAs可通过抑制反应性星形胶质细胞增生和保护AQP4极化而促进年轻鼠脑内胶质淋巴系统对外源性Aβ的清除。而星形胶质细胞增生和AQP4极化率下降是导致老年脑内胶质淋巴系统功能下降的关键因素。因此推测Omega-3 PUFAs可通过改善老年脑内淋巴系统功能而发挥其抗脑衰老作用。本项目拟在多种成像技术平台上，利用多种转基因小鼠，结合代谢组学等技术，明确Omega-3 PUFAs在改善老年脑内淋巴系统功能和抗脑衰老中的作用及机制。本项目的完成对深入理解Omega-3 PUFAs的抗脑衰老机制提供全新的视角，并对研发基于脑内淋巴系统功能的脑衰老早期干预策略，减轻由脑衰老相关疾病所引起的社会负担有着重要的意义。

With the increase of aging population, incidence of brain aging-related diseases showed noticeable gain in recent years, but its pathogenesis is yet to be identified. Studies have shown that the functional impairment of lymphatic drainage system in aged brain might accelerate the process of brain aging, and may be closely related to the development of brain aging-related diseases. Previously, we have confirmed that Omega-3 PUFAs can promote the excretion of exogenous Aβ through the glymphatic system in young mice brain by inhibiting reactive astrocyte proliferation and protecting AQP4 polarization. Interestingly, the reactive astrocyte proliferation and loss of AQP4 polarization is a key factor for the functional impairment of lymphatic drainage system in the aged brain. We thus speculate Omega-3 PUFAs protects against brain aging by improving the function of lymphatic drainage system in aged brain. Using a variety of imaging technology, transgenic mice and Metabolomics, we explore the effects of Omega-3 PUFAs on improving lymphatic drainage system function in the aged brain and on protecting against brain aging. The completion of this project will provide a new perspective on understanding the mechanisms of Omega-3 PUFAs in protecting against brain aging, as well as develop a novel early intervention strategy for brain aging which targets the lymphatic drainage system of brain. It is of important significance in lessening the burdens of brain aging-related disease for patients and community.