微丝骨架调控相分离及细胞衰老的机制研究

人口老龄化严重影响国民健康和社会经济。细胞衰老是造成个体衰老和机能衰退的根本原因，对其机制的研究将有助于加深我们对衰老相关疾病的认识。微丝骨架结构异常是衰老细胞的重要形态学特征，我们的前期工作发现微丝骨架结构可以影响细胞内多种蛋白的相分离过程，而异常相分离形成的大量蛋白聚集体与多种衰老相关疾病具有密切的联系。基于上述证据，我们提出如下假说：衰老细胞的微丝骨架发生异常，干扰了相分离的正常发生，导致了细胞衰老和多种衰老相关疾病的发生。本项目拟采用体外重构体系、单细胞操作、超分辨活细胞动态成像技术结合多组学分析手段，从微丝骨架影响相分离这一新颖角度出发，探究细胞衰老的发生和调控机制。本项目的研究成果将阐明细胞衰老调控的新型分子机制，发现微丝骨架新的生物学功能，为应对衰老及衰老相关疾病提供理论依据。

The trend of population aging in today's world is increasingly obvious, which affects national health and hinders social and economic development. Cell senescence underlies individual aging and decline of physiological function. Mechanistic study of cell senescence will increase our understanding of aging-related diseases. Alterations in the architecture of the actin cytoskeleton are important morphological features of senescent cells. Our preliminary data indicated that the actin cytoskeleton can affect the phase separation process of various proteins in cells. Since formation of a large number of protein aggregates caused by abnormal phase separation is closely related to various aging-related disease. We propose the following hypothesis: the abnormality of the actin cytoskeleton of senescent cells interferes with the normal phase separation process, leading to cell senescence and related diseases. This project intends to combine in vitro remodeling system, single-cell manipulation, super-resolution live cell imaging technology and multi-omics analysis methods to explore the occurrence and regulatory mechanism of cellular aging from the novel perspective of actin-regulated phase separation. The results of this project will help clarify the molecular mechanism of cellular aging regulation, discover new biological functions of the actin cytoskeleton, and provide a theoretical basis for pharmaceutical targeting of aging and aging-related diseases.