Tatar M, Kopelman A, Epstein D, Tu M P, Yin C M, Garofalo R S
Brown University, Providence, RI 02912, USA., University of Massachusetts, Amherst, MA 01003, USA.
Science. 2001 Apr 6;292(5514):107-10. doi: 10.1126/science.1057987.
The Drosophila melanogaster gene insulin-like receptor (InR) is homologous to mammalian insulin receptors as well as to Caenorhabditis elegans daf-2, a signal transducer regulating worm dauer formation and adult longevity. We describe a heteroallelic, hypomorphic genotype of mutant InR, which yields dwarf females with up to an 85% extension of adult longevity and dwarf males with reduced late age-specific mortality. Treatment of the long-lived InR dwarfs with a juvenile hormone analog restores life expectancy toward that of wild-type controls. We conclude that juvenile hormone deficiency, which results from InR signal pathway mutation, is sufficient to extend life-span, and that in flies, insulin-like ligands nonautonomously mediate aging through retardation of growth or activation of specific endocrine tissue.
果蝇的胰岛素样受体（InR）基因与哺乳动物胰岛素受体以及秀丽隐杆线虫的daf-2同源，daf-2是一种调节线虫滞育形成和成虫寿命的信号转导分子。我们描述了一种突变型InR的杂合子、亚效基因型，它会产生体型矮小的雌性果蝇，其成虫寿命延长了85%，还有体型矮小的雄性果蝇，其晚年特定死亡率降低。用保幼激素类似物处理长寿的InR矮小型果蝇，可使其预期寿命恢复到野生型对照的水平。我们得出结论，InR信号通路突变导致的保幼激素缺乏足以延长寿命，并且在果蝇中，胰岛素样配体通过延缓生长或激活特定内分泌组织非自主地介导衰老。
