代谢物α-甲酸通过抑制ATP合成酶和TOR延长寿命
Randall M Chin1, Xudong Fu2, Melody Y Pai3
1Molecular Biology Institute, University of California Los Angeles, Los Angeles, California 90095, USA.
Nature
|May 16, 2014
概括
阿尔法谷氨酸 (α-KG) 是一种代谢物,通过抑制ATP合成酶,延长了C. elegans的寿命. 这一发现揭示了新陈代谢,衰老和饮食限制之间的联系,表明了新的抗衰老策略.
科学领域:
- 代谢学 代谢学 代谢学
- 衰老研究研究 衰老研究
- 线粒体生物学 线粒体生物学
背景情况:
- 饮食限制 (DR) 延长了物种的寿命,并推迟了与年龄相关的疾病.
- 已知影响衰老的代谢物,但它们的机制尚不清楚.
- 阿尔法谷氨酸 (α-KG) 是一种关键的代谢中间体.
研究的目的:
- 研究α-KG在延长寿命中的作用.
- 为了识别α-KG的分子点.
- 阐明α-KG影响衰老和新陈代谢的机制.
主要方法:
- 在Caenorhabditis elegans中进行寿命测定.
- 药物亲和度响应目标稳定性 (DARTS) 用于目标识别.
- 测量ATP含量和氧气消耗.
- 在C. elegans和哺乳动物细胞中进行自的测试.
- 对ATP合成酶和TOR通路的基因操纵.
主要成果:
- α-KG可以延长成年C. elegans的寿命.
- 被确定为一种新的α-KG结合蛋白的ATP合成酶子单元β.
- α-KG抑制ATP合成酶,降低ATP水平和氧气消耗.
- α-KG在C. elegans和哺乳动物细胞中都会诱导自.
- 通过α-KG延长寿命取决于ATP合成酶和TOR途径.
- 内源性α-KG在饥饿期间增加,并调解DR长寿.
结论:
- α-KG是一种通过抑制ATP合成酶延长寿命的代谢物.
- α-KG作为饮食限制诱导的长寿的关键调解者.
- 这项研究揭示了新陈代谢,ATP合成酶和衰老之间的分子联系,表明了新的治疗策略.
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