Lin K, Dorman J B, Rodan A, Kenyon C
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143-0554, USA.
Science. 1997 Nov 14;278(5341):1319-22. doi: 10.1126/science.278.5341.1319.
The wild-type Caenorhabditis elegans nematode ages rapidly, undergoing development, senescence, and death in less than 3 weeks. In contrast, mutants with reduced activity of the gene daf-2, a homolog of the insulin and insulin-like growth factor receptors, age more slowly than normal and live more than twice as long. These mutants are active and fully fertile and have normal metabolic rates. The life-span extension caused by daf-2 mutations requires the activity of the gene daf-16. daf-16 appears to play a unique role in life-span regulation and encodes a member of the hepatocyte nuclear factor 3 (HNF-3)/forkhead family of transcriptional regulators. In humans, insulin down-regulates the expression of certain genes by antagonizing the activity of HNF-3, raising the possibility that aspects of this regulatory system have been conserved.
野生型秀丽隐杆线虫衰老迅速，在不到3周的时间内经历发育、衰老和死亡。相比之下，基因daf-2（胰岛素和胰岛素样生长因子受体的同源物）活性降低的突变体衰老速度比正常情况慢，寿命延长超过两倍。这些突变体活动正常且完全可育，代谢率也正常。daf-2突变引起的寿命延长需要基因daf-16的活性。daf-16似乎在寿命调节中发挥独特作用，编码转录调节因子肝细胞核因子3（HNF-3）/叉头家族的一个成员。在人类中，胰岛素通过拮抗HNF-3的活性来下调某些基因的表达，这增加了这种调节系统的某些方面已经保守的可能性。
