Intestinal Fork Head Regulates Nutrient Absorption and Promotes Longevity.

Bolukbasi, Ekin, Khericha, Mobina, Regan, Jennifer C ORCID: 0000-0003-2164-9151, Ivanov, Dobril K ORCID: 0000-0001-6271-6301, Adcott, Jennifer ORCID: 0000-0001-9146-3171, Dyson, Miranda C ORCID: 0000-0003-0845-662X, Nespital, Tobias, Thornton, Janet M ORCID: 0000-0003-0824-4096, Alic, Nazif ORCID: 0000-0003-0356-6600 and Partridge, Linda ORCID: 0000-0001-9615-0094
(2017) Intestinal Fork Head Regulates Nutrient Absorption and Promotes Longevity. Cell reports, 21 (3). pp. 641-653.

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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
Uncontrolled Keywords: Intestines, Intestinal Mucosa, Enterocytes, Cell Nucleus, Animals, Drosophila melanogaster, Sirolimus, Insulin, Somatomedins, Membrane Transport Proteins, Drosophila Proteins, Nuclear Proteins, Caloric Restriction, Cell Differentiation, Transcription, Genetic, Up-Regulation, Protein Binding, Protein Transport, Oxidative Stress, Phosphorylation, Longevity, Intestinal Absorption, Food, Female, Proto-Oncogene Proteins c-akt, Forkhead Transcription Factors, Insulin Receptor Substrate Proteins
Depositing User: Symplectic Admin
Date Deposited: 15 May 2019 09:43
Last Modified: 17 Mar 2024 21:04
DOI: 10.1016/j.celrep.2017.09.042
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