Wolkow C A, Kimura K D, Lee M S, Ruvkun G
Department of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
Science. 2000 Oct 6;290(5489):147-50. doi: 10.1126/science.290.5489.147.
An insulinlike signaling pathway controls Caenorhabditis elegans aging, metabolism, and development. Mutations in the daf-2 insulin receptor-like gene or the downstream age-1 phosphoinositide 3-kinase gene extend adult life-span by two- to threefold. To identify tissues where this pathway regulates aging and metabolism, we restored daf-2 pathway signaling to only neurons, muscle, or intestine. Insulinlike signaling in neurons alone was sufficient to specify wild-type life-span, but muscle or intestinal signaling was not. However, restoring daf-2 pathway signaling to muscle rescued metabolic defects, thus decoupling regulation of life-span and metabolism. These findings point to the nervous system as a central regulator of animal longevity.
一条类胰岛素信号通路控制着秀丽隐杆线虫的衰老、新陈代谢和发育。daf-2类胰岛素受体基因或下游的age-1磷酸肌醇3激酶基因发生突变，可使成虫寿命延长两到三倍。为了确定该信号通路调节衰老和新陈代谢的组织，我们仅在神经元、肌肉或肠道中恢复daf-2信号通路的信号传递。仅神经元中的类胰岛素信号就足以决定野生型寿命，但肌肉或肠道中的信号则不能。然而，恢复daf-2信号通路在肌肉中的信号传递可挽救代谢缺陷，从而使寿命调节与新陈代谢脱钩。这些发现表明神经系统是动物寿命的核心调节者。
