Figure 5. Mechanisms of action of resveratrol.

Resveratrol promotes mitochondrial biogenesis and functions through indirect AMPK and SIRT1 activation. First, compelling evidence suggests that the metabolic actions of resveratrol are based on its ability to act as a mitochondrial poison by inhibiting ATP synthase activity (1). The resulting energy stress will in turn activate AMPK, leading to the stimulation of SIRT1 by increasing NAD⁺ levels. SIRT1 will then activate downstream targets through deacetylation, ultimately leading to an improvement of mitochondrial function. Another potential explanation of how resveratrol acts is based on a recent report showing that resveratrol inhibits phosphodiesterase (PDE) 4 activity and induces cAMP signaling resulting in Ca²⁺ release and, ultimately the activation of the CamKKb-AMPK pathway (2).