Boehm Michelle, Slack Frank
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, USA.
Science. 2005 Dec 23;310(5756):1954-7. doi: 10.1126/science.1115596.
The microRNA lin-4 and its target, the putative transcription factor lin-14, control the timing of larval development in Caenorhabditis elegans. Here, we report that lin-4 and lin-14 also regulate life span in the adult. Reducing the activity of lin-4 shortened life span and accelerated tissue aging, whereas overexpressing lin-4 or reducing the activity of lin-14 extended life span. Lifespan extension conferred by a reduction in lin-14 was dependent on the DAF-16 and HSF-1 transcription factors, suggesting that the lin-4-lin-14 pair affects life span through the insulin/insulin-like growth factor-1 pathway. This work reveals a role for microRNAs and developmental timing genes in life-span regulation.
微小RNA lin-4及其靶标、假定的转录因子lin-14，控制着秀丽隐杆线虫幼虫发育的时间。在此，我们报告lin-4和lin-14也调节成虫的寿命。降低lin-4的活性会缩短寿命并加速组织衰老，而过度表达lin-4或降低lin-14的活性则会延长寿命。lin-14活性降低所带来的寿命延长依赖于DAF-16和HSF-1转录因子，这表明lin-4-lin-14对通过胰岛素/胰岛素样生长因子-1途径影响寿命。这项研究揭示了微小RNA和发育时间基因在寿命调节中的作用。
