HuR coordinates systemic aging through platelet infiltration. HuR coordinates systemic aging through platelet infiltration

Aging involves morphological and functional changes across different organs, but how these changes are linked among the different organs remains to be elucidated. Here, we uncover a central role of platelets in sys temic aging. In aged mice, the levels of platelet secreted pro inflammatory factors (PSPF) increased greatly in the serum and platelets, leading to a diffuse increase of platelet infiltration in brain, liver, lung, kidney, and aortic root. The RNA binding protein HuR/ELAVL1, a major regulator of R NA metabolism, promoted the production of PSPF in platelets. Platelet specific deletion of HuR reduced the expression of PSPF in platelets, alleviated platelet infiltration in brain, liver, lung, kidney, and aortic root, and delayed systemic aging. Our findings highlight a role of platelets in coordinating aging traits across organs. Overall design: To investigate the function of platelet HuR in systemic aging, we generated a conditional platelet-specific HuR knockout (cKO) mouse. We collected three 25 month-old wild type(WT) and cKO mice liver, lung and brain for single-nucleus RNA sequencing. We then performed gene expression profiling analysis using data obtained from sn-RNA-seq of 3 WT and cKO mice. Comparative gene expression profiling analysis of different cell type from different tissue of sn-RNA-seq data for cKO mice and its WT littermates.

衰老是指机体各器官发生的形态与功能改变，但不同器官间的此类改变如何相互关联仍有待阐明。本研究揭示了血小板在全身衰老过程中的核心作用。在老年小鼠中，血小板分泌促炎因子（platelet secreted pro-inflammatory factors, PSPF）在血清与血小板内的水平显著升高，导致血小板在脑、肝、肺、肾及主动脉根部的浸润呈弥散性增加。RNA结合蛋白HuR/ELAVL1作为RNA代谢的主要调控因子，可促进血小板中PSPF的产生。血小板特异性敲除HuR可降低血小板内PSPF的表达水平，减轻血小板在脑、肝、肺、肾及主动脉根部的浸润，并延缓全身衰老进程。本研究结果凸显了血小板在协调各器官衰老特征中的作用。实验设计：为探究血小板HuR在全身衰老中的功能，我们构建了血小板特异性条件性HuR敲除（cKO）小鼠模型。我们选取3只25月龄的野生型（wild type, WT）与cKO小鼠的肝脏、肺脏及脑组织进行单细胞核RNA测序（single-nucleus RNA sequencing, snRNA-seq）。随后，我们利用3只WT与cKO小鼠的snRNA-seq数据开展基因表达谱分析。对cKO小鼠及其野生型同窝对照小鼠不同组织的不同细胞类型的snRNA-seq数据进行比较基因表达谱分析。