Substrate-specific activation of sirtuins by resveratrol

Kaeberlein M, McDonagh T, Heltweg B, Hixon J, Westman EA, Caldwell SD · Journal of Biological Chemistry

Resveratrol enhanced deacetylation only of peptides carrying the Fluor de Lys fluorescent tag and had no effect on peptides lacking it. In yeast, resveratrol produced no detectable effect on Sir2 activity, silencing or lifespan — the first published challenge to the activator claim.

Population

Purified yeast Sir2 and human SIRT1; three yeast strain backgrounds

Intervention

Resveratrol with fluorophore-tagged versus untagged peptide substrates

Comparator

Untagged acetylated peptides

Limitations

Biochemistry and yeast; says nothing directly about what resveratrol does in a mammalian cell, where activation could still occur indirectly.