Resveratrol — research review 3

...and that’s where resveratrol comes in. It's a polyphenol that activates the NAD-dependent deacetylase SIRT1, essentially mimicking aspects of calorie restriction.

Right, and we've seen some pretty interesting effects in simpler organisms. For example, in yeast, resveratrol extended lifespan by 70% according to a study in Nature back in 2003. It also increased cell survival by stimulating SIRT1-dependent deacetylation of p53.

Exactly. That same 2003 Nature study also noted that resveratrol lowers the Michaelis constant of SIRT1 for its substrates. Beyond yeast, we know resveratrol can trigger autophagy and extend lifespan in nematodes, again via Sirtuin 1, as reported in Aging (Albany NY) in 2009.

And it's not just SIRT1. Resveratrol also activates AMPK, which is another key pathway involved in metabolism and longevity, as highlighted in Current Pharmaceutical Design in 2014. These are all mechanisms linked to the benefits of calorie restriction and even exercise.

Which makes you wonder: do we actually need resveratrol supplements, or can we get these benefits through lifestyle? You mentioned exercise and calorie restriction; they activate similar pathways, so maybe that's the more direct route.

That's the big unknown, isn't it? While resveratrol is found naturally in red grapes, red wine, and peanuts, with wine having the highest concentrations, we still don't have definitive evidence that supplementing with it translates to extended human lifespan or significant health benefits in the way we've seen in lower organisms. The mechanisms are there, but the proof in humans is largely unproven.

So, while the molecule itself is fascinating, the practical applications for human longevity are still very much an open question.