针对Farnesoid X受体作为衰老干预疗法的向
Lijun Zhang1, Jing Yu1, Xiaoyan Gao1
1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Acta pharmaceutica Sinica. B
|May 15, 2025
概括
药物肥酸 (OCA) 可能通过增强排毒途径来延长寿命和健康期. 这种FXR激动剂增加了对有毒物质的抵抗力,并激活了小鼠和虫的排毒基因.
科学领域:
- 衰老和毒理学研究研究.
- 核受体信号传递的信号
- 遗传学和寿命的延长
背景情况:
- 环境中毒物与衰老和与年龄相关的疾病有关.
- 增强的排毒基因表达是各种物种长寿的标记.
- 长寿的动物表现出对有毒物质的抵抗力增加.
研究的目的:
- 为了研究法尔内索伊德X受体 (FXR) 激动剂obeticholic acid (OCA) 延长寿命和健康寿命的潜力.
- 为了确定OCA是否增强了解毒路径和对有毒物质的耐药性.
- 阐明FXR在OCA长寿效应中的作用.
主要方法:
- 用OCA治疗Caenorhabditis elegans和化学诱导的老化小鼠.
- 评估寿命,健康期和耐毒性.
- 对排毒标记物的基因表达分析.
- 在缺乏FXR的小鼠和C. elegans突变的长寿研究.
- 在小鼠肝脏中的代谢分析.
主要成果:
- 在C. elegans和小鼠中,OCA延长了寿命和健康期.
- 在这两种模型中,OCA增强了对有毒物质的抵抗力,并激活了排毒基因.
- 在FXR缺乏或同源突变生物体中,OCA的长寿效应减少.
- 在小鼠肝脏中,OCA增加了内源性孕妇X受体 (PXR) 激素水平.
结论:
- OCA显示出延长寿命和健康的潜力.
- 通过OCA激活FXR,通过增强的排毒促进长寿.
- 针对FXR可能是促进长寿和健康的可行策略.
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