ArticleCell reports2017
Intestinal Fork Head Regulates Nutrient Absorption and Promotes Longevity.
Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 63 citations in OpenAlex.
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- Dietary restriction and lifespan: adaptive reallocation or somatic sacrifice?The FEBS journal · 2023Article
- Sexual identity of enterocytes regulates autophagy to determine intestinal health, lifespan and responses to rapamycin.Nature aging · 2022Article
- Evaluation of lifespan promoting effects of biofortified wheat in Drosophila melanogaster.Experimental gerontology · 2022Article
- SUMOylation of Jun fine-tunes the Drosophila gut immune response.PLoS pathogens · 2022Article
- A nutrient-responsive hormonal circuit mediates an inter-tissue program regulating metabolic homeostasis in adult Drosophila.Nature communications · 2021Article
- FoxO3 deficiency in cortical astrocytes leads to impaired lipid metabolism and aggravated amyloid pathology.Aging cell · 2021Article
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- Cell type-specific modulation of healthspan by Forkhead family transcription factors in the nervous system.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
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.
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Registered trials
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