Challenging the Resveratrol Data
Via In the Pipeline, I see that research groups are suggesting that some of the data for resveratrol (and other possible calorie restriction mimetics developed by Sirtris) is invalid, and previously reported beneficial effects on mice cannot be replicated: "Last fall, a group at Amgen published a study suggesting that some of the SIRT1/resveratrol connections might be due an an experimental artifact caused by a particular fluorescent peptide. Now a group at Pfizer has piled on in the Journal of Biological Chemistry. They're looking over resveratrol and a series of sirtuin activators described by the Sirtris group in Nature. And unfortunately, they also find trouble due to fluorogenic peptides. The TAMRA fluorophore on their peptide substrates seems to pervert the assay. While the Sirtris compounds looked like activators initially, switching to the native peptide substrates showed them to be worthless. Further study (calorimetry) showed that the activator compounds bind to a complex of SIRT1 and the fluorescent peptide substrate, but not to SIRT1 itself (or in the presence of native substrate without the fluorogenic group). That's not good." The researchers also failed to replicate beneficial health effects in their studies on mice. "Basically, these folks have thrown down the gauntlet: they claim that the reported Sirtris compounds do not do what they are claimed to do, neither in vitro nor in vivo, and are worthless as model compounds for anything in this area of study."
Link: http://pipeline.corante.com/archives/2010/01/12/the_sirtris_compounds_worthless_really.php