神经细胞C/EBPβ通过非激活NAMPT缩短寿命
Bowei Li1,2, Zhongyun Xie1, Mengmeng Wang1
1Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, China.
概括
神经中CCAAT/增强剂结合蛋白β (C/EBPβ) 的积累通过降解尼古丁胺酸基转移酶 (NAMPT) 加快衰老. 抑制阿斯巴拉金内酶 (AEP) 或提高NAD+水平可以对抗大脑衰老并延长寿命.
科学领域:
- 神经科学是一个神经科学.
- 衰老研究研究 衰老研究
- 分子生物学分子生物学
背景情况:
- 大脑在衰老和长寿中的作用至关重要,但与年龄相关的认知衰退的机制尚不清楚.
- 神经元功能障碍是衰老的标志,影响整体健康和寿命.
研究的目的:
- 研究神经元CCAAT/增强剂结合蛋白β (C/EBPβ) 在大脑衰老中的作用.
- 确定缓解与年龄相关的神经元衰退和延长寿命的分子标.
主要方法:
- 检查了老年大脑中的C/EBPβ水平及其对尼古丁胺酸转移酶 (NAMPT) 活性的影响.
- 利用转基因小鼠模型 (Thy 1-C/EBPβ) 和C. elegans来研究寿命和认知功能.
- 研究了AEP抑制和NAD+前体补充剂 (NMN) 的作用.
主要成果:
- 神经元C/EBPβ增加驱动衰老和损失,与阿斯巴拉金内酶 (AEP) 和NAD+耗尽的NAMPT碎片化有关.
- 在转基因小鼠中延长了AEP淘汰或AEP耐药NAMPT的寿命.
- 补充NMN或AEP抑制剂#11a改善了老年小鼠的认知和运动功能和寿命.
- #11a在改善衰老表型方面,与NMN相比,显示出更好的治疗效果.
结论:
- 神经元C/EBPβ积累是大脑衰老的关键驱动因素,由AEP诱导的NAMPT降解和NAD+耗尽中介.
- 针对AEP提出了一个有前途的治疗策略,用于打击衰老和与年龄有关的神经系统疾病.
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