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The aryl hydrocarbon receptor promotes aging phenotypes across species

Eckers, Anna, Jakob, Sascha, Heiss, Christian, Haarmann-Stemmann, Thomas, Goy, Christine, Brinkmann, Vanessa, Cortese-Krott, Miriam M., Sansone, Roberto, Esser, Charlotte, Ale-Agha, Niloofar , Altschmied, Joachim, Ventura, Natascia and Haendeler, Judith (2016) The aryl hydrocarbon receptor promotes aging phenotypes across species Scientific Reports, 6 (1), 19618.

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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.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
Eckers, Anna
Jakob, Sascha
Haarmann-Stemmann, Thomas
Goy, Christine
Brinkmann, Vanessa
Cortese-Krott, Miriam M.
Sansone, Roberto
Esser, Charlotte
Ale-Agha, Niloofar
Altschmied, Joachim
Ventura, Natascia
Haendeler, Judith
Date : 21 January 2016
DOI : 10.1038/srep19618
Depositing User : Melanie Hughes
Date Deposited : 16 Aug 2018 09:52
Last Modified : 16 Aug 2018 09:52

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