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This article is part of the supplement: Metabolism, diet and disease

Open Access Poster presentation

Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases

Sung-Jun Park1, Faiyaz Ahmad2, Andrew Philp4, Keith Baar4, Tishan Williams5, Haibin Luo6, Hengming Ke5, Holger Rehmann7, Ronald Taussig8, Alexandra L Brown1, Myung K Kim1, Michael A Beaven3, Alex B Burgin9, Vincent Manganiello2 and Jay H Chung1*

  • * Corresponding author: Jay H Chung

Author Affiliations

1 Laboratory of Obesity and Aging Research, Genetics and Developmental Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA

2 Cardiovascular Pulmonary Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA

3 Laboratory of Molecular Immunology, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA

4 Functional Molecular Biology Laboratory, University of California Davis, Davis, CA 95616, USA

5 Department of Biochemistry and Biophysics, The University of North Carolina, Chapel Hill, NC 27599-7260, USA

6 Structural Biology Lab, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, P. R. China

7 Department of Molecular Cancer Research, Centre for Biomedical Genetics and Cancer Genomics Centre, University Medical Center, 3584 CG Utrecht, The Netherlands

8 Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA

9 Emerald BioStructures, 7869 NE Day Road West, Bainbridge Island, WA 98110, USA

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BMC Proceedings 2012, 6(Suppl 3):P73  doi:10.1186/1753-6561-6-S3-P73


The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1753-6561/6/S3/P73


Published:27 June 2012

© 2012 Park et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Poster presentation

Resveratrol, a polyphenol in red wine, has been reported as a calorie restriction mimetic with potential antiaging and antidiabetogenic properties. It is widely consumed as a nutritional supplement, but its mechanism of action remains a mystery. Here, we report that the metabolic effects of resveratrol result from competitive inhibition of cAMP-degrading phosphodiesterases, leading to elevated cAMP levels. The resulting activation of Epac1, a cAMP effector protein, increases intracellular Ca2+ levels and activates the CamKKβ-AMPK pathway via phospholipase C and the ryanodine receptor Ca2+-release channel. As a consequence, resveratrol increases NAD+ and the activity of Sirt1. Inhibiting PDE4 with rolipram reproduces all of the metabolic benefits of resveratrol, including prevention of diet-induced obesity and an increase in mitochondrial function, physical stamina, and glucose tolerance in mice.