Department of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
Department of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK; Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Strasse 9b, 50931 Cologne, Germany.
Cell Rep. 2014 Feb 27;6(4):608-16. doi: 10.1016/j.celrep.2014.01.015. Epub 2014 Feb 6.
Drosophila melanogaster and Caenorhabditis elegans each carry a single representative of the Forkhead box O (FoxO) family of transcription factors, dFOXO and DAF-16, respectively. Both are required for lifespan extension by reduced insulin/Igf signaling, and their activation in key tissues can extend lifespan. Aging of these tissues may limit lifespan. Alternatively, FoxOs may promote longevity cell nonautonomously by signaling to themselves (FoxO to FoxO) or other factors (FoxO to other) in distal tissues. Here, we show that activation of dFOXO and DAF-16 in the gut/fat body does not require dfoxo/daf-16 elsewhere to extend lifespan. Rather, in Drosophila, activation of dFOXO in the gut/fat body or in neuroendocrine cells acts on other organs to promote healthy aging by signaling to other, as-yet-unidentified factors. Whereas FoxO-to-FoxO signaling appears to be required for metabolic homeostasis, our results pinpoint FoxO-to-other signaling as an important mechanism through which localized FoxO activity ameliorates aging.
果蝇和秀丽隐杆线虫分别携带一个叉头框 O (FoxO)家族转录因子的代表，即 dFOXO 和 DAF-16。它们都需要通过减少胰岛素/IGF 信号来延长寿命，并且它们在关键组织中的激活可以延长寿命。这些组织的衰老可能会限制寿命。或者，FoxO 可能通过自身（FoxO 到 FoxO）或其他因素（FoxO 到其他）在远处组织发出信号，从而促进非自主性长寿细胞。在这里，我们表明，激活果蝇的 dFOXO 和 DAF-16 在肠道/脂肪体中并不需要 dfoxo/daf-16 在其他地方来延长寿命。相反，在果蝇中，激活肠道/脂肪体或神经内分泌细胞中的 dFOXO 通过向其他尚未确定的因素发出信号，作用于其他器官，以促进健康衰老。虽然 FoxO 到 FoxO 的信号似乎是代谢稳态所必需的，但我们的结果指出 FoxO 到其他的信号是局部 FoxO 活性改善衰老的一个重要机制。
