肝脏循环重编程发现了代谢衰老的途径
Shogo Sato1, Guiomar Solanas2, Francisca Oliveira Peixoto2
1Center for Epigenetics and Metabolism, U1233 INSERM, University of California, Irvine, Irvine, CA 92607, USA.
Cell
|August 13, 2017
概括
卡路里限制 (CR) 重新连接昼夜新陈代谢并延长寿命. 这项研究揭示了CR如何影响小鼠的肝脏时钟,蛋白质乙化和衰老,突出显示了该时钟
科学领域:
- 时间生物学与衰老研究
- 代谢平衡和分子机制
背景情况:
- 衰老和昼夜节律是相关的,但外周时钟在代谢衰老中的作用尚不清楚.
- 已知卡路里限制可以延长物种的寿命,并改变生物节能代谢.
研究的目的:
- 研究衰老和卡路里限制如何影响肝脏的昼夜基因表达和新陈代谢.
- 探索昼夜时钟,SIRT1点,NAD+相关代谢物和蛋白质乙化在衰老中的关系.
主要方法:
- 年轻小鼠与老小鼠肝脏,表皮和骨肌肉干细胞中昼夜基因表达的比较分析.
- 在自由食条件下的小鼠与CR条件的评估.
- 对NAD+相关代谢物和全球蛋白质乙化模式的分析.
主要成果:
- 随着年龄的增长,肝脏的昼夜转录组发生了显著的重编程,表现出特定于组织的模式.
- 在肝脏中的SIRT1位中诱导新的振荡基因,以及不同的昼夜代谢特征.
- 衰老导致昼夜蛋白质乙化振荡的缺失,而这种振荡被CR所挽救.
结论:
- 生物钟是蛋白质乙化,肝脏代谢和衰老过程之间的相互作用的核心.
- 可以恢复与年龄相关的昼夜蛋白质乙化下降,这表明寿命延长的机制.
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