Institute of Molecular Medicine, College of Medicine, National Taiwan University, No.7 Chung-Shan South Road, Taipei 10002, Taiwan.
Institute of Molecular Medicine, College of Medicine, National Taiwan University, No.7 Chung-Shan South Road, Taipei 10002, Taiwan.
Dev Cell. 2016 Oct 24;39(2):209-223. doi: 10.1016/j.devcel.2016.08.021. Epub 2016 Oct 6.
Sensory perception, including thermosensation, shapes longevity in diverse organisms, but longevity-modulating signals from the sensory neurons are largely obscure. Here we show that CRH-1/CREB activation by CMK-1/CaMKI in the AFD thermosensory neuron is a key mechanism that maintains lifespan at warm temperatures in C. elegans. In response to temperature rise and crh-1 activation, the AFD neurons produce and secrete the FMRFamide neuropeptide FLP-6. Both CRH-1 and FLP-6 are necessary and sufficient for longevity at warm temperatures. Our data suggest that FLP-6 targets the AIY interneurons and engages DAF-9 sterol hormone signaling. Moreover, we show that FLP-6 signaling downregulates ins-7/insulin-like peptide and several insulin pathway genes, whose activity compromises lifespan. Our work illustrates how temperature experience is integrated by the thermosensory circuit to generate neuropeptide signals that remodel insulin and sterol hormone signaling and reveals a neuronal-endocrine circuit driven by thermosensation to promote temperature-specific longevity.
感觉知觉，包括热觉，塑造了不同生物体的寿命，但感觉神经元传递的长寿调节信号在很大程度上还不清楚。在这里，我们表明，CMK-1/CaMKI 在 AFD 热感觉神经元中对 CRH-1/CREB 的激活是维持秀丽隐杆线虫在温暖温度下寿命的关键机制。响应温度升高和 crh-1 的激活，AFD 神经元产生和分泌 FMRFamide 神经肽 FLP-6。CRH-1 和 FLP-6 都是在温暖温度下长寿所必需和充分的。我们的数据表明，FLP-6 靶向 AIY 中间神经元并参与 DAF-9 固醇激素信号。此外，我们表明，FLP-6 信号下调 ins-7/胰岛素样肽和几种胰岛素途径基因的活性，这些基因的活性损害寿命。我们的工作说明了温度体验如何被热敏电路整合，以产生重塑胰岛素和固醇激素信号的神经肽信号，并揭示了由热敏驱动的神经元-内分泌电路，以促进特定温度的长寿。
