SIRT1通过调节抗氧化反应和抑制细胞衰老来保护脂肪原体的分化
An Yu1,2, Ruofan Yu2, Haiying Liu2
1Yunnan Key Laboratory for Basic Research On Bone and Joint Diseases &, Yunnan Stem Cell Translational Research Center, Kunming University, Kunming, 650214, Yunnan, China.
GeroScience
|July 7, 2023
概括
赛尔图因1 (SIRT1) 对于健康的脂肪细胞分化至关重要,防止细胞衰老,促进中酶干细胞 (MSC) 中的氧化应激反应. 在分化过程中损害SIRT1会导致衰老和代谢功能障碍.
科学领域:
- 细胞生物学 细胞生物学
- 代谢过程中的代谢.
- 衰老研究研究 衰老研究
背景情况:
- 脂肪组织作为内分泌器官,调节新陈代谢和衰老.
- 赛尔图因1 (SIRT1) 是一种依赖NAD+的脱乙酶,已知可以抑制脂肪生成.
- 在介质干细胞 (MSC) 中缺乏SIRT1的小鼠表现出骨质生成缺陷和脂肪组织损失.
研究的目的:
- 为了研究SIRT1在MSCs的脂肪生成差异化中的作用.
- 确定SIRT1抑制对细胞衰老和脂肪生成期间氧化应激的影响.
- 阐明SIRT1在维持脂肪细胞健康方面的新功能.
主要方法:
- 在脂肪基分化过程中抑制MSC中的SIRT1功能.
- 评估细胞衰老标志物 (p16,β-银酸酶活性).
- 对活性氧物种 (ROS) 水平和氧化应激反应途径的分析.
- 对SIRT1目标 (FOXO3,SUV39H1) 和下游信号 (Akt酸化) 的评估.
主要成果:
- 在脂肪生成过程中SIRT1抑制导致显著的缺陷和细胞衰老.
- 在SIRT1抑制后观察到氧化应激反应受损和ROS增加.
- 在MSC特定的SIRT1淘汰赛小鼠中,脂肪组织中的衰老标志物增加.
- SIRT1的点FOXO3和SUV39H1对于健康的脂肪细胞形成至关重要.
- 衰老的脂肪细胞表现出胰岛素敏感性降低和色反应.
结论:
- SIRT1在MSC脂肪基分化中起着关键的保护作用,与其抑制功能不同.
- SIRT1对于控制氧化应激和预防脂肪生成期间衰老至关重要.
- 脂肪细胞中功能障碍的SIRT1有助于代谢障碍,并可能影响癌细胞存活率.
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