Cell· 2012Q1
Resveratrol Ameliorates Aging-Related Metabolic Phenotypes by Inhibiting cAMP Phosphodiesterases
- 1,339citations
- Q1SCImago
- 2012year
Short summary
Resveratrol, a compound found in red wine, combats aging-related metabolic issues by blocking specific enzymes (cAMP phosphodiesterases), which raises crucial cellular energy signals.
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Key points
- Resveratrol's metabolic benefits are due to competitive inhibition of cAMP-degrading phosphodiesterases.
- This inhibition leads to elevated cAMP, activating Epac1, Ca(2+), CamKKβ-AMPK, NAD+, and Sirt1 pathways.
- Inhibiting PDE4 specifically with rolipram replicated resveratrol's positive effects on obesity, mitochondria, stamina, and glucose tolerance in mice.
- These findings suggest PDE4 inhibitors could treat age-related metabolic diseases.
AI-generated from the title and abstract; the full text is not read.
Abstract
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 Ca(2+) levels and activates the CamKKβ-AMPK pathway via phospholipase C and the ryanodine receptor Ca(2+)-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. Therefore, administration of PDE4 inhibitors may also protect against and ameliorate the symptoms of metabolic diseases associated with aging.
The authors' abstract, as published at the source. Cell, 2012 · DOI ↗
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Field: Geriatrics and Gerontology
Geriatrics and GerontologyMedicine