研究背景
杂志名称：Cell Metabolism
影响因子：27.7
文章题目：Exosomal miR-302b rejuvenates aging mice by reversing the proliferative arrest of senescent cells
发表时间：2025年2月4日
研究团队：河南省科学院、中国科学院生物物理研究所姬广聚研究员，薛愿超研究员团队；上海中医药大学博鳌国际医院吴红金教授团队
涉及芯片：QAM-TH17-1（定量检测小鼠Th1/Th2/Th17相关的18个因子芯片）
实验样本：小鼠血清
研究思路
机理模式图
研究结果分析
1. hESC-Exos逆转衰老细胞的增殖停滞
使用复制性衰老的IMR-90细胞（PDL50）和Dox诱导的p21-YFP LO2衰老细胞模型。利用hESC-Exos处理显著降低SA-β-gal活性（衰老标志物），下调CDKN1A（p21）和CDKN2A（p16）表达，并且重塑了细胞增殖状态。
单细胞RNA测序（scRNA-seq）显示，hESC-Exos处理使衰老细胞重新进入细胞周期，S期细胞比例增加17%（图2）
2. hESC-Exos改善衰老小鼠的表型
20月龄小鼠每周接受hESC-Exos或PBS注射，观察至30月龄，hESC-Exos延长小鼠中位寿命，改善运动能力（旋转棒测试、握力测试）和认知功能（水迷宫实验），利用涵盖小鼠炎症免疫等相关的抗体芯片对小鼠血清（QAM-TH17-1）进行检测，发现使用衰老外泌体处理 hESC-Exos 后，促炎性细胞因子的水平显著降低，利用ELISA进一步证明其中IL-1β、IFN-γ、IL-6、TNF-α等因子确实显著降低。
3. miR-302b靶向Cdkn1a和Ccng2逆转衰老
Ago2 Clip-seq分析显示，hESC-Exos富含的miR-302b可直接靶向细胞周期抑制因子Cdkn1a和Ccng2，双荧光素酶实验验证miR-302b与Cdkn1a/Ccng2 3' UTR的结合， miR-302b模拟物处理衰老细胞后，增殖能力恢复，衰老标志物减少。
4. miR-302b长期治疗的安全性及效果
25月龄小鼠每两周接受miR-302b负载的外泌体（Exos-302b）治疗至自然死亡。发现Exos-302b显著延长小鼠寿命（中位寿命增加15.4%），且未增加肿瘤负担。利用抗体芯片（QAM-TH17-1）检测再次验证发现miR-302b小鼠血清中的炎症因子明显降低，结合组织学分析显示，miR-302b减轻衰老相关病理变化，如皮肤增厚和脾脏萎缩。
讨论与总结
创新性：本研究提出“Senoreverse”策略，通过miR-302b逆转SnCs的增殖停滞，实现全身性rejuvenation。研究中同时验证了miR-302b具有治疗衰老及相关疾病的潜力，且长期使用无癌变风险等的安全性。
利用蛋白质芯片等工具高通量测定了衰老病理相关的关键靶标丰度，结合ELISA、组织学等技术验证，多方面支撑了“Senoreverse”策略。
文章信息：
YoukunBi, XinlongQiao, ZhaokuiCai, HailianZhao, RongYe, QunLiu, LinGao, YingqiLiu, BoLiang, YixuanLiu, YaningZhang, ZhiguangYang, YanyunWu, HuiwenWang, WeiJia, ChangqingZeng, CeJia, HongjinWu, YuanchaoXue, GuangjuJi. Exosomal miR-302b rejuvenates aging mice by reversing the proliferative arrest of senescent cells. Cell Metabolism. Volume 37, Issue 2p527-541.e6February 04, 2025. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(24)00481-9
扩展阅读
专题集锦 | 信号通路、蛋白翻译后修饰（PTMs）、肿瘤癌症、肺癌、胃癌、肝癌、胰腺癌、乳腺癌、甲状腺癌、鼻咽癌、结直肠癌、巨噬细胞、自噬、泛素、凋亡、焦亡、铁死亡、免疫、炎症、脓毒症、衰老、阿尔茨海默病、肥胖、糖尿病、肾病、血管生成、心脑血管、肝病、呼吸、结核病、皮肤、眼科、妇科、干细胞、外泌体、类器官、组织工程、骨科、新药研发、中医药、多糖、神奇动物、病毒、麻醉……
【CNS】合集
【衰老】合集
【外泌体】合集
【miroRNA】合集
【单细胞测序】合集
【抗体芯片蛋白组学】合集
【蛋白组学-高通量芯片】合集
【生物医学样本送样手册】合集
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