Cell-nonautonomous effects of dFOXO/DAF-16 in aging

Nazif Alic, Jennifer M. Tullet, Teresa Niccoli, Susan Broughton, Matthew P. Hoddinott, Cathy Slack, David Gems, Linda Partridge*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)608-616
Number of pages9
JournalCell Reports
Volume6
Issue number4
Early online date6 Feb 2014
DOIs
Publication statusPublished - 27 Feb 2014

Bibliographical note

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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