通过部分重编程改善与年龄相关的标志
Alejandro Ocampo1, Pradeep Reddy1, Paloma Martinez-Redondo1
1Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Cell
|December 17, 2016
概括
在小鼠中使用Yamanaka因子 (Oct4,Sox2,Klf4,c-Myc) 的部分重编程可以逆转衰老的特征,延长寿命和改善健康. 这项研究表明,
科学领域:
- 老年学
- 表观遗传学
- 细胞生物学
背景情况:
- 老龄化是许多人类疾病的主要危险因素.
- 在体外研究表明细胞重编程可逆转细胞衰老.
- 在体内证明重编程对衰老过程的影响是有限的.
研究的目的:
- 研究部分细胞重编程对衰老的体内影响.
- 确定OSKM的短期循环表达是否可以改善衰老的特征并延长寿命.
- 评估体内重编程对与年龄相关的生理衰退的影响.
主要方法:
- 在过早衰老的小鼠模型中使用Oct4,Sox2,Klf4和c-Myc (OSKM) 的循环表达进行部分重编.
- 评估细胞和生理衰老的特征.
- 对治疗小鼠的寿命延长的评估.
- 在老野生类型小鼠体内OSKM表达,以评估从代谢疾病和肌肉损伤中恢复.
主要成果:
- 在小鼠中,短期循环OSKM表达改善了细胞和生理衰老的特征.
- 部分重编程延长了小鼠早衰模型的寿命.
- 在老野生小鼠中,OSKM表达改善了代谢疾病和肌肉损伤的恢复.
结论:
- 表观遗传失调是哺乳动物衰老的一个关键因素.
- 在体内部分重编程可以通过表观遗传改造逆转与年龄相关的表型.
- 开发活体平台来调节表观遗传标记对于了解衰老生物学至关重要.
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