Research Paper Volume 13, Issue 1 pp 104—133
Dietary and environmental factors have opposite AhR-dependent effects on C. elegans healthspan
- 1 Leibniz Institute for Environmental Medicine, Auf’m Hennekamp 50, 40225 Düsseldorf, Germany
- 2 Institute of Clinical Chemistry and Laboratory Diagnostic, Heinrich Heine University Düsseldorf, Moorenstr 5, 40225 Düsseldorf, Germany
Received: October 3, 2020 Accepted: November 8, 2020 Published: December 13, 2020https://doi.org/10.18632/aging.202316
How to Cite
Copyright: © 2020 Brinkmann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Genetic, dietary, and environmental factors concurrently shape the aging process. The aryl hydrocarbon receptor (AhR) was discovered as a dioxin-binding transcription factor involved in the metabolism of different environmental toxicants in vertebrates. Since then, the variety of pathophysiological processes regulated by the AhR has grown, ranging from immune response, metabolic pathways, and aging. Many modulators of AhR activity may impact on aging and age-associated pathologies, but, whether their effects are AhR-dependent has never been explored. Here, using Caenorhabditis elegans, as an elective model organism for aging studies, we show for the first time that lack of CeAHR-1 can have opposite effects on health and lifespan in a context-dependent manner. Using known mammalian AhR modulators we found that, ahr-1 protects against environmental insults (benzo(a)pyrene and UVB light) and identified a new role for AhR-bacterial diet interaction in animal lifespan, stress resistance, and age-associated pathologies. We narrowed down the dietary factor to a bacterially extruded metabolite likely involved in tryptophan metabolism. This is the first study clearly establishing C. elegans as a good model organism to investigate evolutionarily conserved functions of AhR-modulators and -regulated processes, indicating it can be exploited to contribute to the discovery of novel information about AhR in mammals.
Aβ: amyloid-beta; AhR: aryl hydrocarbon receptor; AIP: AhR interacting protein (also XAP2); Arnt: AhR nuclear translocator; BaP: benzo(a)pyrene; bHLH/PAS: basic helix–loop–helix/PER–ARNT–SIM; BP: 2,2’Bipyridyl; CYP: cytochrome P450; FICZ: 6-formylindolo[3,2-b]carbazole; GABA: gamma-Aminobutyric acid; Glu: glutamate; GST: glutathione-S-transferase; HSP90: heat shock protein 90; PolyQ: polyglutamine; ROS: reactive oxygen species; TCDD: 2,3,7,8-tetrachlorodibenzodioxin; Trp: tryptophan; UGT: uridine diphosphate glucuronosyl transferase; XRE: xenobiotic responsive element.