间充质干细胞（MSCs）衰老是机体衰老及器官功能退行性改变的重要因素，目前缺乏有效逆转手段。我们前期发现脐带间充质干细胞（UCMSCs）来源的微泡（UCMSC-MVs）体外能逆转老年骨髓MSCs衰老，且能改善自然衰老小鼠骨密度和循环氧化应激水平；进而通过基于测序的差异基因网络分析及干扰实验，初步证实增殖细胞核抗原（PCNA）对MSCs衰老起着核心调控作用，由此推测UCMSC-MVs通过调控PCNA逆转老年骨髓MSCs衰老并改善机体器官功能退行性变化。本项目拟在前期基础上通过体内外实验系统性确证UCMSC-MVs对MSCs衰老及器官功能退行性改变的逆转作用，深入研究其中PCNA扮演的关键角色及其衰老相关的分子调控机制。本项目不仅有望建立基于“年轻”MVs的全新细胞衰老逆转体系，揭示MSCs衰老调控新机制，发现干预靶标和策略，为延缓甚或逆转机体衰老以及脐带的临床转化应用提供新思路。

Cell senescence is key to aging and aging-related degenerative diseases. Research on the current eradication and even reversal of cell aging is very active. We have previously found that umbilical cord mesenchymal stem cells (UCMSCs)-derived microvesicles (UCMSC-MVs) can reverse the senescence of elderly bone marrow MSCs in vitro and improve bone mineral density and circulating oxidative stress in naturally-aging mice. In addition, differential gene network analysis and interference experiments have initially confirmed that proliferating cell nuclear antigen (PCNA) plays a central role in the regulation of senescence of MSCs. Therefore, we speculate that UCMSC-MVs reverse the senescence of MSCs and improve the degeneration of organ function via regulation of PCNA. This project is to systematically confirm the reversal effect of UCMSC-MVs on aging of MSCs and multi-organ function degeneration through in vitro and in vivo experiments, and to study the key role of PCNA and its molecular mechanism related to aging. This project is expected to establish a new aging-reversal system based on "young" MVs, revealing a new mechanism of aging regulation of MSCs, and finding intervention targets and strategies to provide new ideas for delaying or even reversing the aging of the body and clinical application of umbilical cord.