Intestinal Fork Head Regulates Nutrient Absorption and Promotes Longevity.

Bolukbasi, Ekin, Khericha, Mobina, Regan, Jennifer C., Ivanov, Dobril K. ORCID: https://orcid.org/0000-0001-6271-6301, Adcott, Jennifer, Dyson, Miranda C., Nespital, Tobias, Thornton, Janet M., Alic, Nazif and Partridge, Linda 2017. Intestinal Fork Head Regulates Nutrient Absorption and Promotes Longevity. Cell Reports 21 (3) , pp. 641-653. 10.1016/j.celrep.2017.09.042

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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.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Publisher:	Elsevier
ISSN:	2211-1247
Date of First Compliant Deposit:	13 October 2020
Date of Acceptance:	12 September 2017
Last Modified:	05 Jan 2024 04:39
URI:	https://orca.cardiff.ac.uk/id/eprint/135485

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