Kynurenine signaling through the aryl hydrocarbon receptor: Implications for aging and healthspan.

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Tytuł:: Kynurenine signaling through the aryl hydrocarbon receptor: Implications for aging and healthspan.
Autorzy:: Kaiser H; Medical College of Georgia, Augusta University, Augusta, GA 30912, USA. Electronic address: .
Parker E; Medical College of Georgia, Augusta University, Augusta, GA 30912, USA. Electronic address: .
Hamrick MW; Medical College of Georgia, Augusta University, Augusta, GA 30912, USA. Electronic address: .
Źródło:: Experimental gerontology [Exp Gerontol] 2020 Feb; Vol. 130, pp. 110797. Date of Electronic Publication: 2019 Nov 28.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural; Review
Język:: English
Imprint Name(s):: Publication: Tarrytown Ny : Elsevier Science
Original Publication: Oxford.
MeSH Terms:: Longevity*
Aging/*metabolism
Kynurenine/*metabolism
Receptors, Aryl Hydrocarbon/*metabolism
Animals ; Basic Helix-Loop-Helix Transcription Factors ; Humans ; Inflammation ; Mice ; Reactive Oxygen Species/metabolism ; Signal Transduction/physiology ; Tryptophan
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Grant Information:: P01 AG036675 United States AG NIA NIH HHS
Contributed Indexing:: Keywords: Inflammaging; Nrf2; Reactive oxygen species; SLC7A5
Substance Nomenclature:: 0 (AHR protein, human)
0 (Basic Helix-Loop-Helix Transcription Factors)
0 (Reactive Oxygen Species)
0 (Receptors, Aryl Hydrocarbon)
343-65-7 (Kynurenine)
8DUH1N11BX (Tryptophan)
Entry Date(s):: Date Created: 20191202 Date Completed: 20210301 Latest Revision: 20210301
Update Code:: 20240105
PubMed Central ID:: PMC7899131
DOI:: 10.1016/j.exger.2019.110797
PMID:: 31786316
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The tryptophan metabolite kynurenine increases with aging and inflammation, and appears to contribute directly to the development and progression of several age-related conditions. Kynurenine is now known to signal through the aryl hydrocarbon receptor (Ahr) to modulate levels of reactive oxygen species (ROS). The Ahr promoter region contains several sites for NF-kB binding, indicating that inflammation is a key factor modulating Ahr expression. Furthermore, kynurenine activation of Ahr is observed to stimulate expression of the enzyme IDO1, which generates kynurenine by degrading tryptophan, representing a positive feedback loop that may link inflammation with ROS production. On the other hand, the antioxidant system-inducing transcription factor Nrf2 can be stimulated by Ahr, and Nrf2 can itself activate Ahr expression. The balance between pro- and antioxidant functions of Ahr mediated by kynurenine may therefore regulate healthy versus unhealthy aging in different tissues and organ systems. Potential therapeutic approaches to target this pathway include exercise to alter kynurenine production or molecules such as metformin or resveratrol that may suppress Ahr activity.
(Copyright © 2019 Elsevier Inc. All rights reserved.)

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