Elucidation of regulatory mechanism for brain aging

先前的研究表明，较少的神经胰岛素/ IGF-1信号（IIS）延长了哺乳动物和低等动物的寿命并延缓衰老。海马齿状回（DG）中的成年神经发生减少与海马相关的认知功能下降相关，然而，神经IIS减少如何影响认知功能和成年海马神经发生仍然未知。我们发现，增殖和神经元分化显着增强缺乏神经IIS的老年小鼠。此外，神经IIS耗竭抑制老年小鼠DG中树突复杂性和小胶质细胞活化的减少。最后，行为分析表明，缺乏神经IIS的老年小鼠的测试准确率显着高于年龄匹配的对照组。这些发现表明，减少神经IIS可能会延缓大脑衰老。

Previous studies showed that less neural Insulin/ IGF-1 signaling (IIS) extends lifespan and delays aging in mammals as well as in lower animals. Age-related cognitive decline is correlated with the reduced adult neurogenesis in the hippocampal dentate gyrus (DG), however it remained unknown how reduced neural IIS influences cognitive function and adult hippocampal neurogenesis. We found that proliferation and neuronal differentiation remarkably augmented in aged mice lacking neural IIS. Moreover, neural IIS depletion suppressed reduction in dendritic complexity and microglial activation in DG of aged mice. Finally, behavior analysis demonstrated that the test accuracy ratios in aged mice lacking neural IIS were significantly greater than those in age-matched controls. These findings suggest that reduced neural IIS may delay brain aging.