一种类似于药物的分子与核激素受体DAF-12/FXR接触,以调节细胞和延长寿命
Manish Chamoli1, Anand Rane2, Anna Foulger2
1Buck Institute for Research on Aging, Novato, CA, USA. mchamoli@buckinstitute.org.
Nature aging
|November 13, 2023
概括
一种天然化合物,MIC,通过增强自 - lysosomal 功能和mitophagy,延长寿命. 它针对DAF-12/FXR通路,增强线粒体健康,并为与年龄相关的疾病提供潜在的治疗策略.
科学领域:
- 细胞生物学 细胞生物学
- 衰老研究研究 衰老研究
- 药理学 药理学是指药理学的学科.
背景情况:
- 自-溶解体功能对于健康的衰老和疾病预防至关重要.
- 转录因子TFEB调节这种通路,其下降与与年龄相关的疾病有关.
- 针对TFEB为与年龄相关的疾病提供了潜在的治疗途径.
研究的目的:
- 为了确定增强TFEB表达和自-溶解体功能的天然化合物.
- 研究这些化合物的治疗潜力,延长寿命和预防与年龄相关的疾病.
- 阐明已识别的化合物的作用背后的分子机制.
主要方法:
- 对自然产品库进行选,以识别诱导菌的化合物.
- 使用Caenorhabditis elegans来评估寿命延长和对特定遗传途径的依赖 (HLH-30/TFEB,DCT-1/BNIP3).
- 采用哺乳动物细胞模型来评估该化合物对线粒体功能的影响.
- 研究涉及核激素受体DAF-12/FXR的分子机制.
主要成果:
- 发现了诱导神经的氨酸 (MIC),一种增强TFEB表达和溶酶体功能的氨酸.
- 在C. elegans中,MIC通过HLH-30/TFEB和线粒细胞吸收 (涉及DCT-1/BNIP3) 显著延长了C. elegans的寿命.
- MIC 防止哺乳动物细胞中的线粒体功能障碍,并通过抑制 DAF-12 / FXR 激活来延长寿命,从而诱导线粒体.
结论:
- MIC是一种有前途的类似药物的分子,可以增强线粒体功能并延长寿命.
- MIC通过抑制DAF-12/FXR而起作用,导致线粒和寿命延长.
- DAF-12/FXR被确定为HLH-30/TFEB和线粒细胞的新兴上游调节剂.
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