The question about resveratrol’s health benefits does not solely depend on whether resveratrol directly or indirectly activates SIRT1 or not. In fact, recent studies have determined that resveratrol appears to activate other SIRT genes. For example, resveratrol increases SIRT3, which recent research has shown is the key regulator for cellular energy produced by mitochondria.63

Still other studies indicate that inhibiting SIRT1 did not lessen resveratrol’s antioxidant protection against free radical stress on neurons. Nor did inactivation of SIRT1 stop resveratrol from helping to resolve plaque formation in an experimental model for Alzheimer’s disease.64

AMPK and Resveratrol

Perhaps clarifying some of the contradictory study results on both resveratrol and SIRT1 is recent research showing that resveratrol triggers AMP-activated protein kinase (AMPK).65 This enzyme plays a key role in regulating cellular energy (both consumption and production), gene activation, and other metabolic processes (e.g., insulin production and metabolism of sugars, fats, and proteins).66

Stimulating this important enzyme can have an enormous beneficial impact on health, and studies have shown that AMPK activation by resveratrol protects mitochondria in cells from malfunction caused by free radical damage.67 One animal study shows that resveratrol’s activation of AMPK in the brain reduces amyloid-β (Aβ) peptide levels—the proteins that create the brain plaques characteristic of Alzheimer’s disease and degeneration of brain cells.68

Resveratrol May Indirectly Activate SIRT1

Interestingly, there are now studies that contradict the protective value of SIRT1 against neurological damage—including some that suggest that substances that inhibit SIRT1 could protect neurons and that SIRT1 itself could make neurons more likely to die.64-65 When SIRT1 is activated it lowers levels of the enzyme nicotinamide adenine nucleotide (NAD+) and blocking SIRT1 activity after injury maintains NAD+, which studies show limits the death of damaged neurons.64

An expert from the National University of Singapore School of Medicine theorizes that by activating AMPK resveratrol indirectly increases SIRT1 activity—but after it takes care of the immediate toxic situation dangerous to brain neurons.65 Although there needs to be further research to clarify exactly how and when resveratrol works in conjunction with sirtuins to either inhibit or enhance certain physiological functions and activity, there seems to be no dispute that resveratrol does function in ways that are beneficial to our health.18,26

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