Evidence for a common mechanism of SIRT1 regulation by allosteric activators

Hubbard BP, Gomes AP, Dai H, Li J, Case AW, Considine T · Science

The counter-argument: hydrophobic motifs in natural SIRT1 substrates such as PGC-1alpha and FOXO3a permit activation without any fluorophore, and a single residue (Glu230) was required for activation by every activator class tested. In cells carrying activation-defective SIRT1, the metabolic effects of these compounds were abolished.

Population

Purified SIRT1, primary cells reconstituted with mutant SIRT1

Intervention

Resveratrol and other sirtuin-activating compounds against native substrates

Comparator

Activation-defective SIRT1 (E230K)

Limitations

In vitro and primary cells; several authors were affiliated with Sirtris/GSK, the company built on sirtuin-activating compounds, which the paper discloses.