by Nils Osmar. April 1, 2022
Resveratrol (found in grapes, red wine and blueberries) has been promoted as a potent anti-aging supplement; an activator of the sirtuin 1 gene; and an activator of AMPK (the longevity pathway). Dr. David Sinclair has said that it also appears to extends lifespan in lab animals, but that more research is needed to determine whether it has that effect in humans.
Not all researchers accept the premise that it’s a potent SIRT1 activator (or even that there’s a benefit to activating the sirtuins, if it does). But most research to date supports the conclusion that it does, and that it has additional health benefits.
Is it the world’s best sirtuin gene activator? Based on the studies I’ve read, I would say no. It’s reliable, but not a record=breaker. Sinclair has said that oleic acid is far more effective at activating the sirtuin 1 gene than resveratrol, Quercetin and fisetin have a similar, though weaker, sirtuin-activating effect. Sinclair has also said that resveratrol is poorly absorbed, so should be taken along with some protein or fat to enhance absorption.
So why take it?
You’ll have to decide if it makes sense for you to take resveratrol. I’m continuing to do so, for a number of reasons.
In a study called “Resveratrol upregulates SIRT1 and inhibits cellular oxidative stress in the diabetic milieu: mechanistic insights“, the authors conclude that it does activate SIRT1, and write,
Many studies reported that resveratrol possessed various bioactivities, such as antioxidant, anti-inflammatory, cardiovascular protection, anticancer, antidiabetes mellitus, antiobesity, neuroprotection, and antiaging effects.
The antiaging mechanisms of resveratrol were mainly ameliorating oxidative stress, relieving inflammatory reaction, improving mitochondrial function, and regulating apoptosis….
The authors of a study called “Effects and Mechanisms of Resveratrol on Aging and Age-Related Diseases” agree, and write:
The antiaging mechanisms of resveratrol were mainly ameliorating oxidative stress, relieving inflammatory reaction, improving mitochondrial function, and regulating apoptosis. Resveratrol could be an effective and safe compound for the prevention and treatment of aging and age-related diseases.
In a study called “Resveratrol supplementation at old age reverts changes associated with aging in inflammatory, oxidative and apoptotic markers in rat heart“, the authors wrote:
Resveratrol reverted age-related changes in inflammatory, oxidative and apoptotic markers in the rat heart.
Among others, the expression of two major inflammatory markers, INF-γ and TNF-α and two oxidative markers, heme oxygenase-1 and nitric oxide synthase, were increased with aging, and resveratrol supplementation reduced the level of some of these to those observed in the heart of young animals. Moreover, age-related changes in apoptotic markers in rat heart tend to be also reverted by resveratrol treatment.
Conclusion: Our results suggest that resveratrol might exert beneficial effects as an anti-aging compound to revert age-related changes in cardiac function.
This summary cites over a hundred recent studies, and concludes that:
Resveratrol induces mitochondrial biogenesis and protects against metabolic decline. In obese rodents, treatment with resveratrol improves metabolic and vascular function, decreases hepatic steatosis, reduces inflammation, increases endurance, and supports gene expression in a way that’s similar to calorie restriction
Recent studies have shown that resveratrol also confers metabolic benefits in humans, including activating AMPK (the s0-called longevity pathway). (Its benefits are not limited to lab animals.) (AMPK is also activated by activities that increase cellular stress, including fasting and intense physical exercise exercise.)
Re: its effects on mitochondria, a study called “SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function” lists a number of ways that it supports mitochondrial functioning, and concludes that:“One of the most robust and reproducible effects of resveratrol treatment is an increase in mitochondrial mass.”
But does activating SIRT1 really extend lifespan? The studies are inconclusive. As Mike Lustgarten points out in this video, activating SIRT6 may have a much greater impact on lifespan.
(Note: SIRT6 is NAD+-dependent. For this reason, I take it along with NMN and NR, which raise NAD+ levels in the body.)
What I’m Doing
I take resveratrol, not so much because I believe it will make me live longer — it may or may not turn out to have that effect in humans — as for its pro-health and anti-aging effects. (Anti-aging compounds can benefit our health in numerous ways regardless of whether they lengthen the lifespan.)
I take it to support my mitochondria; because it may be protective against cancer and heart disease because it detoxifies nitrites in processed foods; and for its other health benefits, I usually take it along with a few bites of avocado to make sure that I’m absorbing it.
I also take products such as SIRT6 activator and black elderberry extract to activate my sirtuin 6 gene, which shows evidence of a greater life-extending effect.
Sinclair has said that the mice in his lab studies appeared to live longer if given resveratrol every other day instead of every other day. For this reason, I’m taking it three days a week.