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Intestinal Fork Head Regulates Nutrient Absorption and Promotes Longevity

Bolukbasi, E; Khericha, M; Regan, JC; Ivanov, DK; Adcott, J; Dyson, MC; Nespital, T; ... Partridge, L; + view all (2017) Intestinal Fork Head Regulates Nutrient Absorption and Promotes Longevity. Cell Reports , 21 (3) pp. 641-653. 10.1016/j.celrep.2017.09.042. Green open access

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Abstract

Reduced activity of nutrient-sensing signaling networks can extend organismal lifespan, yet the underlying biology remains unclear. We show that the anti-aging effects of rapamycin and reduced intestinal insulin/insulin growth factor (IGF) signaling (IIS) require the Drosophila FoxA transcription factor homolog Fork Head (FKH). Intestinal FKH induction extends lifespan, highlighting a role for the gut. FKH binds to and is phosphorylated by AKT and Target of Rapamycin. Gut-specific FKH upregulation improves gut barrier function in aged flies. Additionally, it increases the expression of nutrient transporters, as does lowered IIS. Evolutionary conservation of this effect of lowered IIS is suggested by the upregulation of related nutrient transporters in insulin receptor substrate 1 knockout mouse intestine. Our study highlights a critical role played by FKH in the gut in mediating anti-aging effects of reduced IIS. Malnutrition caused by poor intestinal absorption is a major problem in the elderly, and a better understanding of the mechanisms involved will have important therapeutic implications for human aging.

Type: Article
Title: Intestinal Fork Head Regulates Nutrient Absorption and Promotes Longevity
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2017.09.042
Publisher version: https://doi.org/10.1016/j.celrep.2017.09.042
Language: English
Additional information: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Science & Technology, Life Sciences & Biomedicine, Cell Biology, RESTRICTION-INDUCED LONGEVITY, LIFE-SPAN EXTENSION, C-ELEGANS, DROSOPHILA-MELANOGASTER, SIGNALING PATHWAY, TISSUE HOMEOSTASIS, IMMUNE-RESPONSE, GENE-EXPRESSION, GROWTH-FACTOR, FAT-BODY
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: http://discovery.ucl.ac.uk/id/eprint/10036557
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