College of Life Science and Technology, Key Laboratory of Molecular Biophysics of MOE, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China.
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Nat Aging. 2021 Mar;1(3):255-268. doi: 10.1038/s43587-021-00039-1. Epub 2021 Mar 15.
The role of food nutrients in mediating the positive effect of dietary restriction (DR) on longevity has been extensively characterized, but how non-nutrient food components regulate lifespan is not well understood. Here, we show that food-associated odors shorten the lifespan of under DR but not those fed , revealing a specific effect of food odors on DR-mediated longevity. Food odors act on a neural circuit comprising the sensory neurons ADF and CEP, and the interneuron RIC. This olfactory circuit signals the gut to suppress DR-mediated longevity via octopamine, the invertebrate homolog of norepinephrine, by regulating the energy sensor AMPK through a Gq-PLCβ-CaMKK-dependent mechanism. In mouse primary cells, we find that norepinephrine signaling regulates AMPK through a similar mechanism. Our results identify a brain-gut axis that regulates DR-mediated longevity by relaying olfactory information about food abundance from the brain to the gut.
食物营养在介导饮食限制 (DR) 对长寿的积极影响方面的作用已经得到了广泛的研究，但非营养性食物成分如何调节寿命还不是很清楚。在这里，我们发现与食物相关的气味会缩短 的寿命，而不会缩短 的寿命，这表明食物气味对 DR 介导的寿命有特定的影响。食物气味作用于一个由感觉神经元 ADF 和 CEP 以及中间神经元 RIC 组成的神经回路。这个嗅觉回路通过调节能量传感器 AMPK 来抑制 DR 介导的长寿，其机制是通过 Gq-PLCβ-CaMKK 依赖的机制来调节昆虫同源物去甲肾上腺素的活性。在小鼠原代细胞中，我们发现去甲肾上腺素信号通过类似的机制调节 AMPK。我们的研究结果确定了一个脑-肠轴，它通过将食物丰度的嗅觉信息从大脑传递到肠道来调节 DR 介导的长寿。
