细胞非自主激活含有黄素的单氧酶促进长寿和健康寿命
Scott F Leiser1, Hillary Miller1, Ryan Rossner1
1Department of Pathology, University of Washington, Seattle, WA 98195, USA.
Science (New York, N.Y.)
|November 21, 2015
概括
在神经元中稳定缺氧诱导因子1 (HIF-1) 通过肠道信号激活排毒酶FMO-2延长了线虫的寿命. 这种涉及血清素的途径与饮食限制相结合,
科学领域:
- 分子生物学
- 遗传学
- 老龄化研究
背景情况:
- 已知低氧诱导因子1 (HIF-1) 稳定可以延长线虫的寿命和健康期.
- 这些延长寿命的潜在机制在很大程度上是未知的.
研究的目的:
- 阐明神经元 HIF-1 稳定延长 Caenorhabditis elegans 的寿命的机制.
- 确定参与HIF-1中介寿命的信号通路和分子参与者.
主要方法:
- 在C. elegans中对神经元特异性的HIF-1稳定.
- 从神经元到肠道的细胞非自主信号的分析.
- 研究血清生物合成和信号通路的作用.
- 评估含有黄素的单氧酶-2 (FMO-2) 对寿命的作用.
主要成果:
- 神经性HIF-1稳定通过向肠道发送非自主信号延长寿命.
- 这种信号激活了含有黄素的排毒酶单氧酶-2 (FMO-2).
- 延长寿命信号需要神经元TPH-1和肠道SER-7,突出显示了血清素信号的作用.
- 肠道FMO-2激活也由饮食限制 (DR) 诱导,对于DR介导的寿命延长至关重要.
结论:
- 神经性HIF-1稳定通过保存的胺依赖通路激活肠道FMO-2延长了C. elegans的寿命.
- FMO-2 作为 HIF-1 和饮食限制寿命路径的融合点.
- 这些发现表明食动物在促进包括哺乳动物在内的各种物种的健康和长寿方面发挥着至关重要的作用.
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