Resveratrol and Drug Discovery

Resveratrol, whose chemical structure is shown on the left, is not a house-hold name yet. But it may very well be one, maybe in a year or so. Published data demontrated that it could extend the life-span of yeast, worm, fly, fish, and mice up to 20-50%. At such a grand evolution scale, it seems to me its effect on human should be very promising.

The mechanism of resveratrol was proposed to involve an enzyme called sertuin, which removes a acyl group (CH3CO-) from an acyl-lysine sidechain in a protein. Cell uses the acylation/deacylation, much in the same way as phosphorylation/dephophorylation, to regulate many crucial activities. The physical basis all involve introduce/eliminate a charge in a protein so that a significant reorganization of the protein structure would take place and thus function differently. The enzyme needs help from NAD+ in order to do the job, a mechanism nature has designed to link the acylation/deacylation to metabolism. That's because NAD+ and its reducing form NADH, especially their concentration ratio reflects how well an animal is fed - more NADH means more food, vice versa, because the energy in the food is converted to the reducing power of NADH, which is then used to reduce O2 gas breathed in to generate energy that every cell can use - ATP. Resveratrol was shown to increase the activity of sertuin, thus mimicing the effect of increasing NAD+/NADH ratio, thus mimicing the starvation condition, the only proved way of extending life span of a primate. Most of the research I presented in the paragraph came from a Harvard group. So far so good.

But some scientists disagree the above mechanism - one group from U of Minesota and another one from U of Washington. They said the effect of resveratrol is ARTIFICIAL - it only increase the sirtuin activity when the artificial substrate - a peptide embeded with an fluorophore. Their data is frustating for those who like to extend their life or their youth life by taking resveratrol. Of course, resveratrol could still have effect even though its mechanism through activating sirtuin proves to be wrong. Other posible mechanism includes well-known anti-oxidant. So far, I am unable to tell who is right who is wrong.