Volume 6 Supplement 3

Metabolism, diet and disease

Open Access

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
BMC Proceedings20126(Suppl 3):P73

DOI: 10.1186/1753-6561-6-S3-P73

Published: 27 June 2012

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.

Authors’ Affiliations

Laboratory of Obesity and Aging Research, Genetics and Developmental Biology Center, National Heart Lung and Blood Institute, National Institutes of Health
Cardiovascular Pulmonary Branch, National Heart Lung and Blood Institute, National Institutes of Health
Laboratory of Molecular Immunology, National Heart Lung and Blood Institute, National Institutes of Health
Functional Molecular Biology Laboratory, University of California Davis
Department of Biochemistry and Biophysics, The University of North Carolina
Structural Biology Lab, School of Pharmaceutical Sciences, Sun Yat-sen University
Department of Molecular Cancer Research, Centre for Biomedical Genetics and Cancer Genomics Centre, University Medical Center
Department of Pharmacology, University of Texas Southwestern Medical Center
Emerald BioStructures


© Park et al; licensee BioMed Central Ltd. 2012

This article is published under license to 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.