Institute of Healthy Ageing and GEE, University College London, UK.
Aging Cell. 2010 Jun;9(3):336-46. doi: 10.1111/j.1474-9726.2010.00558.x. Epub 2010 Feb 12.
Dietary restriction extends lifespan in diverse organisms, but the gene regulatory mechanisms and tissues mediating the increased survival are still unclear. Studies in worms and flies have revealed a number of candidate mechanisms, including the target of rapamycin and insulin/IGF-like signalling (IIS) pathways and suggested a specific role for the nervous system in mediating the response. A pair of sensory neurons in Caenorhabditis elegans has been found to specifically mediate DR lifespan extension, but a neuronal focus in the Drosophila nervous system has not yet been identified. We have previously shown that reducing IIS via the partial ablation of median neurosecretory cells in the Drosophila adult brain, which produce three of the seven fly insulin-like peptides, extends lifespan. Here, we show that these cells are required to mediate the response of lifespan to full feeding in a yeast dilution DR regime and that they appear to do so by mechanisms that involve both altered IIS and other endocrine effects. We also present evidence of an interaction between these mNSCs, nutrition and sleep, further emphasising the functional homology between the DILP-producing neurosecretory cells in the Drosophila brain and the hypothalamus of mammals in their roles as integration sites of many inputs for the control of lifespan and behaviour.
饮食限制能延长多种生物的寿命，但介导这种生存能力提高的基因调控机制和组织仍不清楚。在蠕虫和苍蝇中的研究揭示了一些候选机制，包括雷帕霉素靶蛋白和胰岛素/胰岛素样生长因子信号通路，并表明神经系统在介导反应中具有特定作用。在秀丽隐杆线虫中，一对感觉神经元被发现可以特异性介导 DR 寿命延长，但在果蝇神经系统中尚未确定特定的神经元焦点。我们之前已经表明，通过部分切除成年果蝇大脑中的中脑神经分泌细胞来降低 IIS，这些细胞产生七种果蝇胰岛素样肽中的三种，可以延长寿命。在这里，我们表明，这些细胞是介导酵母稀释 DR 饮食限制下寿命对完全喂养反应所必需的，它们似乎通过涉及改变 IIS 和其他内分泌作用的机制来发挥作用。我们还提供了这些 mNSCs 与营养和睡眠之间相互作用的证据，进一步强调了果蝇大脑中产生 DILP 的神经分泌细胞和哺乳动物下丘脑在作为控制寿命和行为的许多输入的整合位点方面的功能同源性。
