Explaining Rat Red-wine Superpowers

Resveratrol, found in small amounts in red wine, is well-known to protect mice from aging and obesity. It’s not yet known whether it works in humans (it’s expensive enough that you wouldn’t want to just take a bunch of it on speculation). There are some synthetic resveratrol analogues already developed in research, but again, they’re not cheaply available (nor assuredly free of side effects).

A fantastic series of experiments isolates the mechanism for the (in rats) benefits of the resveratrol-like family, confirming suspicions that it functions by activating a protein involved in energy metabolism, SIRT1*

1. answer an objection (that an artificial fluourescent marker used in test tube studies linking resveratrol turned out to be necessary for the reaction to occur) by locating the third ingredient existing in the rat cells (tryptophan, a common amino acid, turned out to suffice).

2. generate modified versions of SIRT1 by playing with mouse genes (because synthesizing organic chemicals is tricky; if you just want randomly different versions, you can do this by fuzzing genes of organisms that produce it**). It’s expensive to analyze a complicated molecule, so they just looked at the gene versions (out of 2000 they generated) that had no benefit from resveratrol, and found some minimal change to the structure of regular SIRT1 that disables the effect. This is almost certainly where resveratrol acts on SIRT1.

3. Using one of their 2000 mutant lines that blocked the resveratrol effect, they tried all the resveratrol-analogues, and found that none of them worked. This adds a little confidence that the analogues all work by the same mechanism.

4. finally, they verify the results in (mouse) skin and muscle cells by replacing the normal SIRT1 gene w/ their mutant variant, and showing that this blocked the resveratrol benefit (they should have done a “placebo” version of this where they replace it with the normal version). I wonder why they can’t do this for human cells? We mostly care if this can benefit humans.

I wonder if enhancing SIRT1 will turn out to have harms as well as benefits. If not, then it can only be because producing resveratrol wasn’t conveniently available as a mutation in mammals. We could also ask why we don’t produce more SIRT1, even if we don’t have a multiplier available to enhance its effectiveness. I’d guess that producing SIRT1 is expensive.

*  It’s interesting that resveratrol enhances SIRT1 activity, because it’s harder to find a chemical that speeds up a protein’s good functions than it is to find one that interferes (usually by binding to the useful location to deny it to other parties).

** although you don’t necessarily build a full organism; it looks like they fuzzed the genes but did the reactions in a test tube?

via (Science, so it’s peer reviewed)