title: The aryl hydrocarbon receptor promotes aging phenotypes across species.
abstract: The ubiquitously expressed aryl hydrocarbon receptor (AhR) induces drug metabolizing enzymes as well as regulators of cell growth, differentiation and apoptosis. Certain AhR ligands promote atherosclerosis, an age-associated vascular disease. Therefore, we investigated the role of AhR in vascular functionality and aging. We report a lower pulse wave velocity in young and old AhR-deficient mice, indicative of enhanced vessel elasticity. Moreover, endothelial nitric oxide synthase (eNOS) showed increased activity in the aortas of these animals, which was reflected in increased NO production. Ex vivo, AhR activation reduced the migratory capacity of primary human endothelial cells. AhR overexpression as well as treatment with a receptor ligand, impaired eNOS activation and reduced S-NO content. All three are signs of endothelial dysfunction. Furthermore, AhR expression in blood cells of healthy human volunteers positively correlated with vessel stiffness. In the aging model Caenorhabditis elegans, AhR-deficiency resulted in increased mean life span, motility, pharynx pumping and heat shock resistance, suggesting healthier aging. Thus, AhR seems to have a negative impact on vascular and organismal aging. Finally, our data from human subjects suggest that AhR expression levels could serve as an additional, new predictor of vessel aging.
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine, 40225 Duesseldorf, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Eckers
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine, 40225 Duesseldorf, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: Jakob
authors.affiliation: Division of Cardiology, Pulmonary Diseases, Vascular Medicine, Medical Faculty, University Duesseldorf, 40225 Duesseldorf, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine, 40225 Duesseldorf, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Haarmann-Stemmann
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine, 40225 Duesseldorf, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Goy
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine, 40225 Duesseldorf, Germany.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Brinkmann
authors.affiliation: Division of Cardiology, Pulmonary Diseases, Vascular Medicine, Medical Faculty, University Duesseldorf, 40225 Duesseldorf, Germany.
authors.forename: Miriam M
authors.initials: MM
authors.lastname: Cortese-Krott
authors.affiliation: Division of Cardiology, Pulmonary Diseases, Vascular Medicine, Medical Faculty, University Duesseldorf, 40225 Duesseldorf, Germany.
authors.forename: Roberto
authors.initials: R
authors.lastname: Sansone
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine, 40225 Duesseldorf, Germany.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Esser
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine, 40225 Duesseldorf, Germany.
authors.forename: Niloofar
authors.initials: N
authors.lastname: Ale-Agha
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine, 40225 Duesseldorf, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Altschmied
authors.affiliation: Central Institute of Clinical Chemistry and Laboratory Medicine, Medical Faculty, University of Duesseldorf, 40225 Duesseldorf, Germany.|IUF-Leibniz Research Institute for Environmental Medicine, 40225 Duesseldorf, Germany.
authors.forename: Natascia
authors.initials: N
authors.lastname: Ventura
authors.affiliation: Central Institute of Clinical Chemistry and Laboratory Medicine, Medical Faculty, University of Duesseldorf, 40225 Duesseldorf, Germany.|IUF-Leibniz Research Institute for Environmental Medicine, 40225 Duesseldorf, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Haendeler
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008136:Longevity / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010641:Phenotype; D010766:Phosphorylation; D063177:Pulse Wave Analysis; D019655:Quantitative Trait, Heritable; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists / Q000235:genetics* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D018336:Receptors, Aryl Hydrocarbon; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III