title: Cell-nonautonomous effects of dFOXO/DAF-16 in aging.
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.
authors: Department of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
authors: Nazif
authors: N
authors: Alic
authors: Department of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
authors: Jennifer M
authors: JM
authors: Tullet
authors: Department of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
authors: Teresa
authors: T
authors: Niccoli
authors: Department of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
authors: Susan
authors: S
authors: Broughton
authors: 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.
authors: Matthew P
authors: MP
authors: Hoddinott
authors: Department of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
authors: Cathy
authors: C
authors: Slack
authors: Department of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
authors: David
authors: D
authors: Gems
authors: 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. Electronic address: l.partridge@ucl.ac.uk.
authors: Linda
authors: L
authors: Partridge
mesh_terms: D000375:Aging; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005216:Fat Body / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D008136:Longevity; D055099:Neuroendocrine Cells / Q000378:metabolism; D009928:Organ Specificity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D029721:Drosophila Proteins; C477334:FOXO protein, Drosophila; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; C108831:daf-16 protein, C elegans