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

Helen Kaiser, Emily Parker, Mark W. Hamrick

Research output: Contribution to journalReview article

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number110797
JournalExperimental Gerontology
Volume130
DOIs
StatePublished - Feb 2020

Keywords

  • Inflammaging
  • Nrf2
  • Reactive oxygen species
  • SLC7A5

ASJC Scopus subject areas

  • Biochemistry
  • Aging
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Cell Biology

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