在衰老过程中,神经菌抑制了细胞质mtDNA依赖cGAS/STING炎症的激活
Juan Ignacio Jiménez-Loygorri1, Beatriz Villarejo-Zori1, Álvaro Viedma-Poyatos1
1Department of Cellular and Molecular Biology, Centro de Investigaciones Biológicas Margarita Salas, CSIC, Madrid, Spain.
Nature communications
|January 27, 2024
概括
线粒体,去除受损的线粒体,不会随着年龄的增长而减少,但可能会增加. 用urolithin A诱导线粒会减少炎症,并改善老年小鼠的健康状况.
科学领域:
- 细胞生物学 细胞生物学
- 衰老研究研究 衰老研究
- 免疫学 免疫学 免疫学
背景情况:
- 细胞中的一个关键过程 - - 宏自,随着年龄的增长而下降,是衰老的标志.
- 线粒体的与年龄相关的变化,即通过自选择性去除线粒体,仍然在很大程度上没有表征.
- 了解线粒在衰老中的作用对于开发促进健康衰老的干预措施至关重要.
研究的目的:
- 为了调查线粒细胞衰减是否随着年龄的增长而下降.
- 探索衰老,线粒和炎症途径之间的关系.
- 评估线粒细胞诱导在缓解与年龄相关的衰退中的治疗潜力.
主要方法:
- 利用 mito-QC 记者小鼠模型来评估年轻和老小鼠在各个器官中的线粒.
- 在老老鼠的视网膜组织上进行了转录基因分析,以确定分子变化.
- 检查了来自老年捐赠者的原发性人体纤维细胞,以在人类环境中验证发现.
- 给老小鼠注射乌罗素A以药理学上诱导线粒并评估其影响.
主要成果:
- 与预期相反,在老老小鼠和年轻小鼠中,甲状腺食被发现要么增加,要么不变.
- 老老鼠在视网膜中表现出I型干扰素反应的上调,这与细胞质线粒体DNA (mtDNA) 和cGAS/STING通路激活的增加有关.
- 这些与年龄相关的炎症变化在老年人的人体纤维细胞中成功复制.
- 在老小鼠中,用urolithin A药理上诱导了线粒,导致cGAS/STING激活的减弱和神经功能的改善.
结论:
- 线粒体似乎不会随着年龄的增长而减少;相反,与年龄相关的线粒体功能障碍可能会引发补偿性线粒体.
- 该研究确定了衰老,细胞质mtDNA增加,cGAS/STING通路激活和I型干扰素反应之间的联系.
- 线粒诱导,以urolithin A治疗为例,是减少与年龄相关的炎症和增强健康的有前途的治疗策略.
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