SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1

Pacholec M, Bleasdale JE, Chrunyk B, et al. · The Journal of Biological Chemistry

The standing challenge to the 'SIRT1 activator' label: with native, untagged substrates, resveratrol produced no apparent SIRT1 activation — activation appeared only with a fluorophore-tagged peptide, and the compounds were shown to interact with the fluorophore tag itself. Direct activation, the premise of the resveratrol-plus-NAD+-precursor pairing, is disputed at the biochemical level.

Population

Biochemical assays of purified SIRT1 with native peptide and full-length protein substrates (p53, acetyl-CoA synthetase 1)

Intervention

Resveratrol and the SRT-series compounds tested for direct SIRT1 activation

Comparator

The fluorophore-tagged peptide substrate used in the original activation assays

Limitations

In-vitro biochemistry from a Pfizer group; does not rule out indirect SIRT1 activation in cells (e.g., upstream signalling), which remains an open debate. Abstract states both assay conditions verbatim; full text paywalled.