Resveratrol is not a direct activator of SIRT1 enzyme activity
Abstract
Resveratrol is a plant polyphenol capable of exerting beneficial metabolic effects which are thought to be mediated in large by the activation of the NAD + ‐dependent protein deacetylase SIRT1. Although resveratrol has been claimed to be a bona fide SIRT1 activator using a peptide substrate (Fluor de Lys‐SIRT1 peptide substrate), recent reports indicate that this finding might be an experimental artifact and need to be clarified. Here, we show that: (i) the Fluor de Lys‐SIRT1 peptide is an artificial SIRT1 substrate because in the absence of the covalently linked fluorophore the peptide itself is not a substrate of the enzyme, (ii) resveratrol does not activate SIRT1 in vitro in the presence of either a p53‐derived peptide substrate or acetylated PGC‐1α isolated from cells, and (iii) although SIRT1 deacetylates PGC‐1α in both in vitro and cell‐based assays, resveratrol did not activate SIRT1 under these conditions. Based on these observations, we conclude that the pharmacological effects of resveratrol in various models are unlikely to be mediated by a direct enhancement of the catalytic activity of the SIRT1 enzyme. In consequence, our data challenge the overall utility of resveratrol as a pharmacological tool to directly activate SIRT1.
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Resveratrol may not directly activate SIRT1 but acts through AMPK, though direct SIRT1 activation is not fully excluded.
“Recently, it was shown, however, that resveratrol may not activate SIRT1 directly (Beher et al., 2009; Pacholec et al., 2010), but rather exerts its effects on SIRT1 through activation of AMPK (Baur et al., 2006; Canto et al., 2009; Canto et al., 2010; Feige et al., 2008; Hawley et al., 2010; Um et al., 2010), although additional direct SIRT1 activation is not completely excluded (Dai et al., 2010”
From Calorie Restriction-like Effects of 30 Days of Resveratrol Supplementation on Energy Metabolism and Metabolic Profile in Obese Humans (2011) · cites this paper as Beher et al., 2009
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Self-citation
- Authors
- Beher, D., Wu, J., Cumine, S., Kim, K. W., Lu, S., Atangan, L., & Wang, M.
- Affiliations
- Amgen (United States) (US)
- Corresponding author
- Wang, Minghan
- Venue
- Chemical Biology & Drug Design
- Publisher
- Wiley
- Published
- 2009-10-28
- Volume
- 74
- Issue
- 6
- Pages
- 619-624
- ISSN
- 1747-0277 (ISSN-L)
- 1747-0285
- OpenAlex
- W2018951168
- Cited by
- 426
- References
- 21
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 6 · 2023: 5 · 2022: 7 · 2021: 23 · 2020: 20 · 2019: 19 · 2018: 18 · 2017: 20 · 2016: 18 · 2015: 22 · 2014: 38 · 2013: 48 · 2012: 51
- FWCI
- 39.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Chemical Biology & Drug Design (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- resveratrol, SIRT1, SIRT1 activation, NAD+-dependent deacetylase, PGC-1α, protein deacetylation, polyphenols, metabolic effects
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Resveratrol, Acetylation, Cell Line, Heat-Shock Proteins, Humans, Peptides, Recombinant Fusion Proteins, Stilbenes, Transcription Factors, RNA, Small Interfering, Sirtuin 1
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