恢复骨髓细胞的新陈代谢可以逆转衰老的认知能力
Paras S Minhas1,2,3, Amira Latif-Hernandez1, Melanie R McReynolds4,5
1Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Nature
|January 21, 2021
概括
通过向骨髓细胞中的前列腺素E2 (PGE2) 信号,通过恢复细胞能量代谢和减少炎症来逆转与年龄相关的认知衰退. 这种方法可以恢复老鼠的大脑功能和记忆力.
科学领域:
- 免疫学
- 神经科学
- 代谢过程
背景情况:
- 衰老与慢性炎症有关, 导致阿尔茨海默病和认知衰退等疾病.
- 导致年龄相关炎症的确切机制及其对大脑功能的影响尚未完全理解.
- 前列腺素E2 (PGE2) 是一个关键的脂质媒介,参与炎症.
研究的目的:
- 调查前列腺素E2 (PGE2) 信号在老化过程中的骨髓细胞生物能量的作用.
- 确定抑制PGE2信号是否可以逆转与年龄相关的认知衰退和炎症.
- 探索针对骨髓细胞代谢进行认知复苏的潜力.
主要方法:
- 在老年小鼠中研究骨髓细胞的生物能量.
- 研究了通过EP2受体传递前列腺素E2 (PGE2) 对葡萄糖代谢和线粒体功能的影响.
- 给老鼠使用EP2受体抑制剂.
- 评估了细胞生物能量,炎症标志物,突触可塑性和空间记忆.
主要成果:
- 由于PGE2信号的增加,衰老抑制了骨髓细胞的生物能量,导致葡萄糖被封存到糖原中,并减少了线粒体呼吸.
- 这种老骨髓细胞的能量缺陷促进了炎症反应.
- 抑制骨髓状EP2信号,使细胞生物能量再生,减少全身和大脑炎症,改善海马突触可塑性和空间记忆.
- 阻断外围骨髓EP2信号恢复了老鼠的认知功能.
结论:
- 通过重编程骨髓糖代谢, 认知衰老可能是可逆的.
- 针对骨髓质EP2信号提供了一个治疗策略, 以恢复年轻的免疫功能并逆转认知衰退.
- 这项研究强调了骨髓细胞代谢,炎症和认知衰老之间的关键联系.
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