Cited by 745Sirtuins and Resveratrol in MedicineGenetics, Aging, and Longevity in Model OrganismsHistone Deacetylase Inhibitors Research

Substrate-specific activation of sirtuins by resveratrol

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Kaeberlein, Matt, McDonagh, Thomas, Heltweg, Birgit, Hixon, Jeffrey, Westman, Eric A., Caldwell, Seth D., Napper, Andrew, Curtis, Rory +4 more·2005·Journal of Biological Chemistry

Abstract

Resveratrol, a small molecule found in red wine, is reported to slow aging in simple eukaryotes and has been suggested as a potential calorie restriction mimetic. Resveratrol has also been reported to act as a sirtuin activator, and this property has been proposed to account for its anti-aging effects. We show here that resveratrol is a substrate-specific activator of yeast Sir2 and human SirT1. In particular, we observed that, in vitro, resveratrol enhances binding and deacetylation of peptide substrates that contain Fluor de Lys, a non-physiological fluorescent moiety, but has no effect on binding and deacetylation of acetylated peptides lacking the fluorophore. Consistent with these biochemical data we found that in three different yeast strain backgrounds, resveratrol has no detectable effect on Sir2 activity in vivo, as measured by rDNA recombination, transcriptional silencing near telomeres, and life span. In light of these findings, the mechanism accounting for putative longevity effects of resveratrol should be reexamined.

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Crossref · 10.1074/jbc.m500655200

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  • Fluorophore-coupled substrates have been questioned in several contexts.

    “Finally, because fluorophore-coupled substrates have been questioned in several contexts (Kaeberlein et al., 2005; Toro et al., 2017), we validated the preference for demyristoylation over deacetylation using non-fluorogenic peptides ( 7 -9 ) in an LC-MS-based assay (Fig. 2B).”

    From Histone deacetylase 11 is an ε-N-Myristoyllysine hydrolase (2018) · cites this paper as Kaeberlein et al., 2005

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Authors
Kaeberlein, M., McDonagh, T., Heltweg, B., Hixon, J., Westman, E. A., Caldwell, S. D., Napper, A., Curtis, R., DiStefano, P. S., Fields, S., Bedalov, A., & Kennedy, B. K.
Affiliations
  • University of Washington (US)
  • Fred Hutch Cancer Center (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
  • Bedalov, Antonio
  • Kennedy, Brian K.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2005-04
Volume
280
Issue
17
Pages
17038-17045
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2102646072
Cited by
745
References
68
Citations by year
2026: 14 · 2025: 7 · 2024: 11 · 2023: 15 · 2022: 15 · 2021: 22 · 2020: 23 · 2019: 29 · 2018: 27 · 2017: 23 · 2016: 46 · 2015: 42 · 2014: 41 · 2013: 66 · 2012: 74
FWCI
18.55
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Institute on Aging (P30AG013280)
Topics
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
Keywords
resveratrol, sirtuins, Sir2, SIRT1, deacetylation, peptide substrates, caloric restriction mimetics, aging, longevity
MeSH terms
Resveratrol, Antioxidants, Binding, Competitive, DNA, Ribosomal, Dose-Response Relationship, Drug, Fungal Proteins, Histone Deacetylases, Humans, Kinetics, Models, Chemical, Niacinamide, Peptides, Protein Binding, Recombination, Genetic, Stilbenes, Substrate Specificity, Time Factors, Transcription, Genetic, Tumor Suppressor Protein p53, Telomere, Gene Silencing, Sirtuins, Silent Information Regulator Proteins, Saccharomyces cerevisiae, Sirtuin 1, Sirtuin 2, Histone Deacetylase Inhibitors, In Vitro Techniques

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