Substrate-specific activation of sirtuins by resveratrol
Open accessAbstract
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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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
Cites
Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan
Howitz, K. T., Bitterman, K. J., Cohen, H. Y., Lamming, D. W., Lavu, S., Wood, J. G., Zipkin, R. E., Chung, P., Kisielewski, A., Zhang, L.-L., et al. (2003) · Nature · doi:10.1038/nature01960 · Cited by 3,796 · see citing works
Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
Imai, S.-I., Armstrong, C. M., Kaeberlein, M., & Guarente, L. (2000) · Nature · doi:10.1038/35001622 · Cited by 3,510 · see citing works
Self-citationModulation of NF‐κB‐dependent transcription and cell survival by the SIRT1 deacetylase
Yeung, F., Hoberg, J. E., Ramsey, C. S., Keller, M. D., Jones, D. R., Frye, R. A., & Mayo, M. W. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600244 · Cited by 2,750 · see citing works
hSIR2SIRT1 Functions as an NAD-Dependent p53 Deacetylase
Vaziri, H., Dessain, S. K., Eaton, E. N., Imai, S., Frye, R. A., Pandita, T. K., Guarente, L., & Weinberg, R. A. (2001) · Cell · doi:10.1016/s0092-8674(01)00527-x · Cited by 2,653 · see citing works
Boeke, J. D., Lacroute, F., & Fink, G. R. (1984) · Molecular and General Genetics MGG · doi:10.1007/bf00330984 · Cited by 2,354 · see citing works
Kaeberlein, M., McVey, M., & Guarente, L. (1999) · Genes & Development · doi:10.1101/gad.13.19.2570 · Cited by 2,253 · see citing works
Self-citationNegative Control of p53 by Sir2α Promotes Cell Survival under Stress
Luo, J., Nikolaev, A. Y., Imai, S.-I., Chen, D., Su, F., Shiloh, A., Guarente, L., & Gu, W. (2001) · Cell · doi:10.1016/s0092-8674(01)00524-4 · Cited by 2,081 · see citing works
Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-γ
Picard, F., Kurtev, M. V., Chung, N., Topark‐Ngarm, A., Senawong, T., de Oliveira, R. M., Leid, M. E., McBurney, M. W., & Guarente, L. (2004) · Nature · doi:10.1038/nature02583 · Cited by 1,943 · see citing works
Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans
Tissenbaum, H. A., & Guarente, L. (2001) · Nature · doi:10.1038/35065638 · Cited by 1,918 · see citing works
Sirtuin activators mimic caloric restriction and delay ageing in metazoans
Wood, J. G., Rogina, B., Lavu, S., Howitz, K., Helfand, S. L., Tatar, M., & Sinclair, D. (2004) · Nature · doi:10.1038/nature02789 · Cited by 1,868 · see citing works
Lin, S.-J., Defossez, P.-A., & Guarente, L. (2000) · Science · doi:10.1126/science.289.5487.2126 · Cited by 1,775 · see citing works
Extrachromosomal rDNA circles—a cause of aging in yeast
Sinclair, D. A., & Guarente, L. (1997) · Cell · doi:10.1016/s0092-8674(00)80493-6 · Cited by 1,500 · see citing works
The Sir2 Family of Protein Deacetylases
Blander, G., & Guarente, L. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.011303.073651 · Cited by 1,480 · see citing works
Rates of Behavior and Aging Specified by Mitochondrial Function During Development
Dillin, A., Hsu, A.-L., Arantes-Oliveira, N., Lehrer-Graiwer, J., Hsin, H., Fraser, A. G., Kamath, R. S., Ahringer, J., & Kenyon, C. (2002) · Science · doi:10.1126/science.1077780 · Cited by 1,121 · see citing works
Increased Nuclear NAD Biosynthesis and SIRT1 Activation Prevent Axonal Degeneration
Araki, T., Sasaki, Y., & Milbrandt, J. (2004) · Science · doi:10.1126/science.1098014 · Cited by 1,060 · see citing works
Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration
Lin, S.-J., Kaeberlein, M., Andalis, A. A., Sturtz, L. A., Defossez, P.-A., Culotta, V. C., Fink, G. R., & Guarente, L. (2002) · Nature · doi:10.1038/nature00829 · Cited by 1,057 · see citing works
Self-citationBitterman, K. J., Anderson, R. M., Cohen, H. Y., Latorre-Esteves, M., & Sinclair, D. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205670200 · Cited by 1,002 · see citing works
The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases
Landry, J., Sutton, A., Tafrov, S. T., Heller, R. C., Stebbins, J., Pillus, L., & Sternglanz, R. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.110148297 · Cited by 970 · see citing works
A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity
Lee, S. S., Lee, R. Y. N., Fraser, A. G., Kamath, R. S., Ahringer, J., & Ruvkun, G. (2003) · Nature Genetics · doi:10.1038/ng1056 · Cited by 969 · see citing works
Extension of Life-Span with Superoxide Dismutase/Catalase Mimetics
Melov, S., Ravenscroft, J., Malik, S., Gill, M. S., Walker, D. W., Clayton, P., Wallace, D. C., Malfroy, B., Doctrow, S. R., & Lithgow, G. J. (2000) · Science · doi:10.1126/science.289.5484.1567 · Cited by 913 · see citing works
Rine, J., & Herskowitz, I. (1987) · Genetics · doi:10.1093/genetics/116.1.9 · Cited by 711 · see citing works
Aparicio, O. M., Billington, B. L., & Gottschling, D. E. (1991) · Cell · doi:10.1016/0092-8674(91)90049-5 · Cited by 704 · see citing works
Boulton, S. J., & Jackson, S. P. (1998) · The EMBO Journal · doi:10.1093/emboj/17.6.1819 · Cited by 641 · see citing works
Cancer Chemopreventive Activity of Resveratrol
Bhat, K. P. L., & Pezzuto, J. (2002) · Drugs under experimental and clinical research · doi:10.1111/j.1749-6632.2002.tb02918.x · Cited by 633 · see citing works
Calorie restriction extends yeast life span by lowering the level of NADH
Lin, S.-J., Ford, E., Haigis, M., Liszt, G., & Guarente, L. (2004) · Genes & Development · doi:10.1101/gad.1164804 · Cited by 632 · see citing works
An unusual form of transcriptional silencing in yeast ribosomal DNA.Preprint
Smith, J. S., & Boeke, J. D. (1997) · Genes & Development · doi:10.1101/gad.11.2.241 · Cited by 588 · see citing works
Tanner, K. G., Landry, J. W., Sternglanz, R., & Denu, J. M. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.250422697 · Cited by 557 · see citing works
Gottlieb, S., & Esposito, R. E. (1989) · Cell · doi:10.1016/0092-8674(89)90681-8 · Cited by 545 · see citing works
Determination of Life-Span in Caenorhabditis elegans by Four Clock Genes
Lakowski, B., & Hekimi, S. (1996) · Science · doi:10.1126/science.272.5264.1010 · Cited by 539 · see citing works
Grozinger, C. M., Chao, E. D., Blackwell, H. E., Moazed, D., & Schreiber, S. L. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106779200 · Cited by 533 · see citing works
Relocalization of telomeric Ku and SIR proteins in response to DNA strand breaks in yeast
Martin, S. G., Laroche, T., Suka, N., Grunstein, M., & Gasser, S. M. (1999) · Cell · doi:10.1016/s0092-8674(00)80773-4 · Cited by 464 · see citing works
Inhibition of mitochondrial proton F0F1‐ATPase/ATP synthase by polyphenolic phytochemicals
Zheng, J., & Ramirez, V. D. (2000) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0703397 · Cited by 453 · see citing works
Sir2-Independent Life Span Extension by Calorie Restriction in Yeast
Kaeberlein, M., Kirkland, K. T., Fields, S., & Kennedy, B. K. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020296 · Cited by 441 · see citing works
Self-citationElimination of Replication Block Protein Fob1 Extends the Life Span of Yeast Mother Cells
Defossez, P., Prusty, R., Kaeberlein, M. R., Lin, S.-J., Ferrigno, P. K., Silver, P. A., Keil, R., & Guarente, L. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80472-4 · Cited by 401 · see citing works
Self-citationTranscriptional silencing of Ty1 elements in the RDN1 locus of yeast.Preprint
Bryk, M., Banerjee, M., Murphy, M. N., Knudsen, K. E., Garfinkel, D. J., & Curcio, M. J. (1997) · Genes & Development · doi:10.1101/gad.11.2.255 · Cited by 373 · see citing works
Identification of a small molecule inhibitor of Sir2p
Bedalov, A., Gatbonton, T., Irvine, W. P., Gottschling, D. E., & Simon, J. A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.261574398 · Cited by 344 · see citing works
Self-citationMills, K. D., Sinclair, D. A., & Guarente, L. (1999) · Cell · doi:10.1016/s0092-8674(00)80772-2 · Cited by 334 · see citing works
Cloning and characterization of four SIR genes of Saccharomyces cerevisiae.
Ivy, J. M., Klar, A. J. S., & Hicks, J. B. (1986) · Molecular and Cellular Biology · doi:10.1128/mcb.6.2.688 · Cited by 294 · see citing works
A Fluorogenic Histone Deacetylase Assay Well Suited for High-Throughput Activity Screening
Wegener, D., Wirsching, F., Riester, D., & Schwienhorst, A. (2003) · Chemistry & Biology · doi:10.1016/s1074-5521(02)00305-8 · Cited by 283 · see citing works
Effects of stilbenes on arachidonate metabolism in leukocytes
Kimura, Y., Hiromichi, O., & Arichi, S. (1985) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(85)90167-5 · Cited by 273 · see citing works
Effects of resveratrol on the rat brain respiratory chain.
Zini, R., Morin, C., Bertelli, A., Bertelli, A., & Tillement, J. P. (1999) · PubMed · Cited by 252 · see citing works
Extension of Life-Span in Caenorhabditis elegans by a Diet Lacking Coenzyme Q
Larsen, P. L., & Clarke, C. F. (2002) · Science · doi:10.1126/science.1064653 · Cited by 249 · see citing works
MicroReview: Small molecules that regulate lifespan: evidence for xenohormesis
Lamming, D. W., Wood, J. G., & Sinclair, D. A. (2004) · Molecular Microbiology · doi:10.1111/j.1365-2958.2004.04209.x · Cited by 231 · see citing works
Borra, M. T., Langer, M. R., Slama, J. T., & Denu, J. M. (2004) · Biochemistry · doi:10.1021/bi049592e · Cited by 214 · see citing works
Resveratrol acts as a natural profungicide and induces self‐intoxication by a specific laccase
Schouten, A., Wagemakers, L., Stefanato, F. L., et al. (2002) · Molecular Microbiology · doi:10.1046/j.1365-2958.2002.02801.x · Cited by 184 · see citing works
Effect of vitamin E on lifespan and reproduction in Caenorhabditis elegans
Harrington, L. A., & Harley, C. B. (1988) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(88)90098-x · Cited by 169 · see citing works
Inhibitors of Sir2: Evaluation of Splitomicin Analogues
Posakony, J., Hirao, M., Stevens, S. D., Simon, J. A., & Bedalov, A. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm030473r · Cited by 160 · see citing works
Self-citationPark, P. U., Defossez, P.-A., & Guarente, L. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.5.3848 · Cited by 155 · see citing works
Kaeberlein, M. R., Andalis, A. A., Fink, G. R., & Guarente, L. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.22.8056-8066.2002 · Cited by 143 · see citing works
Self-citationAntioxidant activity of resveratrol in red wine
Miller, N. J., & Rice-Evans, C. A. (1995) · Clinical Chemistry · doi:10.1093/clinchem/41.12.1789 · Cited by 116 · see citing works
Zheng, J., & Ramirez, V. D. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.1063 · Cited by 100 · see citing works
Inhibition sites in F1-ATPase from bovine heart mitochondria
Gledhill, J. R., & Walker, J. E. (2005) · Biochemical Journal · doi:10.1042/bj20041513 · Cited by 96 · see citing works
Diversity in the Sir2 family of protein deacetylases
Buck, S. W., Gallo, C. M., & Smith, J. S. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.0903424 · Cited by 93 · see citing works
N-Acetylcysteine slows down ageing and increases the life span of Drosophila melanogaster
Brack, C., Bechter-Thüring, E., & Labuhn, M. (1997) · Cellular and Molecular Life Sciences · doi:10.1007/pl00013199 · Cited by 92 · see citing works
Large-scale identification in yeast of conserved ageing genes
Kaeberlein, M. R., & Kennedy, B. K. (2004) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2004.09.013 · Cited by 78 · see citing works
Self-citationHirao, M., Posakony, J., Nelson, M., Hruby, H., Jung, M., Simon, J. A., & Bedalov, A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308966200 · Cited by 73 · see citing works
Self-citationPleiotropic effects of resveratrol
Granados‐Soto, V. (2003) · Drug News & Perspectives · doi:10.1358/dnp.2003.16.5.829318 · Cited by 71 · see citing works
Saccharomyces cerevisiae SSD1-V Confers Longevity by a Sir2p-Independent Mechanism
Kaeberlein, M. R., Andalis, A. A., Liszt, G. B., Fink, G. R., & Guarente, L. (2004) · Genetics · doi:10.1534/genetics.166.4.1661 · Cited by 57 · see citing works
Self-citationArmstrong, C. M., Kaeberlein, M. R., Imai, S., & Guarente, L. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.01-10-0482 · Cited by 55 · see citing works
Self-citationSIR2 and aging – the exception that proves the rule
Guarente, L. (2001) · Trends in Genetics · doi:10.1016/s0168-9525(01)02339-3 · Cited by 49 · see citing works
Quantitative Assays for Characterization of the Sir2 Family of NAD+-Dependent Deacetylases
Borra, M. T., & Denu, J. M. (2003) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(03)76011-x · Cited by 42 · see citing works
More on antioxidant activity of resveratrol in red wine
Goldberg, D. M. (1996) · Clinical Chemistry · doi:10.1093/clinchem/42.1.113 · Cited by 38 · see citing works
Intracellular targeting and functional analysis of single-chain Fv fragments in mammalian cells
Cardinale, A. (2004) · Methods · doi:10.1016/j.ymeth.2004.04.006 · Cited by 32 · see citing works
Prolongation of Life in an Experimental Model of Aging in Drosophila Melanogaster
Jordens, R. G., Berry, M. D., Gillott, C., & Boulton, A. A. (1999) · Neurochemical Research · doi:10.1023/a:1022510004220 · Cited by 26 · see citing works
Effect of butylated hydroxytoluene on the life span of Drosophila bipectinata
Sharma, S., & Wadhwa, R. (1983) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(83)90099-4 · Cited by 25 · see citing works
Society for biomolecular screening
Giordano, C. (1996) · Drug Discovery Today · doi:10.1016/1359-6446(96)89036-2 · Cited by 11 · see citing works
Life Span Studies in Zaprionus paravittigerwith Sodium Hypophosphite Feeding
Wadhwa, R., Rai, N., & Sharma, S. (2009) · Gerontology · doi:10.1159/000212780 · Cited by 7 · see citing works
Effect of Sodium Selenite on Antioxidative Enzymes of Banana Fruitfly
Kaur, M., Wadhwa, R., & Sharma, S. (2009) · Gerontology · doi:10.1159/000213021 · Cited by 7 · see citing works
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Therapeutic potential of resveratrol: the in vivo evidence
Baur, J. A., & Sinclair, D. A. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd2060 · Cited by 3,958 · see citing works
Epigenetics and the environment: emerging patterns and implications
Feil, R., & Fraga, M. F. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3142 · Cited by 1,929 · see citing works
Price, N. L., Gomes, A. P., Ling, A. J. Y., Duarte, F. V., Martin-Montalvo, A., North, B. J., Agarwal, B., Ye, L., Ramadori, G., Teodoro, J. S., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.003 · Cited by 1,602 · see citing works
Regulation of Yeast Replicative Life Span by TOR and Sch9 in Response to Nutrients
Kaeberlein, M., Powers, R. W., Steffen, K. K., Westman, E. A., Hu, D., Dang, N., Kerr, E. O., Kirkland, K. T., Fields, S., & Kennedy, B. K. (2005) · Science · doi:10.1126/science.1115535 · Cited by 1,293 · see citing works
Self-citationSRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1
Pacholec, M., Bleasdale, J. E., Chrunyk, B., Cunningham, D., Flynn, D., Garofalo, R. S., Griffith, D., Griffor, M., Loulakis, P., Pabst, B., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.088682 · Cited by 915 · see citing works
Rapamycin, But Not Resveratrol or Simvastatin, Extends Life Span of Genetically Heterogeneous Mice
Miller, R. A., Harrison, D. E., Astle, C. M., Baur, J. A., Boyd, A. R., de Cabo, R., Fernandez, E., Flurkey, K., Javors, M. A., Nelson, J. F., et al. (2011) · The Journals of Gerontology: Series A · doi:10.1093/gerona/glq178 · Cited by 896 · see citing works
Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds
Bonkowski, M. S., & Sinclair, D. A. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.93 · Cited by 834 · see citing works
Sauve, A. A., Wolberger, C., Schramm, V. L., & Boeke, J. D. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.74.082803.133500 · Cited by 763 · see citing works
Luen Tang, B. (2016) · Molecules and Cells · doi:10.14348/molcells.2016.2318 · Cited by 740 · see citing works
AMP-activated protein kinase-deficient mice are resistant to the metabolic effects of resveratrol
Um, J.-H., Park, S.-J., Kang, H., Yang, S., Foretz, M., McBurney, M. W., Kim, M. K., Viollet, B., & Chung, J. H. (2010) · Diabetes · doi:10.2337/db09-0482 · Cited by 647 · see citing works
Sirtuins in aging and age-related disease
Longo, V. D., & Kennedy, B. K. (2006) · Cell · doi:10.1016/j.cell.2006.07.002 · Cited by 628 · see citing works
Self-citationAbsence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila
Burnett, C., Valentini, S., Cabreiro, F., Goss, M., Somogyvári, M., Piper, M. D., Hoddinott, M., Sutphin, G. L., Leko, V., McElwee, J. J., et al. (2011) · Nature · doi:10.1038/nature10296 · Cited by 624 · see citing works
Self-citationBarger, J. L., Kayo, T., Vann, J. M., Arias, E. B., Wang, J., Hacker, T. A., Wang, Y., Raederstorff, D., Morrow, J. D., Leeuwenburgh, C., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002264 · Cited by 580 · see citing works
Guarente, L. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1100831 · Cited by 510 · see citing works
AMPK at the Nexus of Energetics and Aging
Burkewitz, K., Zhang, Y., & Mair, W. B. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.03.002 · Cited by 483 · see citing works
The molecular targets of resveratrol
Kulkarni, S. S., & Cantó, C. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.10.005 · Cited by 477 · see citing works
Sirtuin activators and inhibitors: Promises, achievements, and challenges
Dai, H., Sinclair, D. A., Ellis, J. L., & Steegborn, C. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.03.004 · Cited by 463 · see citing works
“Initially, the observation that no activation is obtained for resveratrol or early generation synthetic STACs when the fluorophore of the FdL substrate peptide is removed (Borra et al., 2005; Kaeberlein et al., 2005) had elicited controversies on Sirtuin activation.”
BackgroundCalorie restriction and sirtuins revisited
Guarente, L. (2013) · Genes & Development · doi:10.1101/gad.227439.113 · Cited by 464 · see citing works
Targeting Sirtuin 1 to Improve Metabolism: All You Need Is NAD+?
Cantó, C., & Auwerx, J. (2012) · Pharmacological Reviews · doi:10.1124/pr.110.003905 · Cited by 433 · see citing works
Resveratrol is not a direct activator of SIRT1 enzyme activity
Beher, D., Wu, J., Cumine, S., Kim, K. W., Lu, S., Atangan, L., & Wang, M. (2009) · Chemical Biology & Drug Design · doi:10.1111/j.1747-0285.2009.00901.x · Cited by 426 · see citing works
Capiralla, H., Vingtdeux, V., Zhao, H., Sankowski, R., Al‐Abed, Y., Davies, P., & Marambaud, P. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07594.x · Cited by 426 · see citing works
Neuroprotective Mechanisms of Resveratrol in Alzheimer’s Disease: Role of SIRT1
Gomes, B. A. Q., Silva, J. P. B., Romeiro, C. F. R., dos Santos, S. M., Rodrigues, C. A., Gonçalves, P. R., Sakai, J. T., Mendes, P. F. S., Varela, E. L. P., & Monteiro, M. C. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/8152373 · Cited by 403 · see citing works
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Secondary metabolism in cannabis
Flores-Sanchez, I. J., & Verpoorte, R. (2008) · Phytochemistry Reviews · doi:10.1007/s11101-008-9094-4 · Cited by 400 · see citing works
Sirtuin functions and modulation: from chemistry to the clinic
Carafa, V., Rotili, D., Forgione, M., Cuomo, F., Serretiello, E., Hailu, G. S., Jarho, E., Lahtela-Kakkonen, M., Mai, A., & Altucci, L. (2016) · Clinical Epigenetics · doi:10.1186/s13148-016-0224-3 · Cited by 387 · see citing works
A review: using nanoparticles to enhance absorption and bioavailability of phenolic phytochemicals
Li, Z., Jiang, H., Xu, C., & Gu, L. (2015) · Food Hydrocolloids · doi:10.1016/j.foodhyd.2014.05.010 · Cited by 376 · see citing works
Cardiac Aging: From Molecular Mechanisms to Significance in Human Health and Disease
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The Sir2 family of protein deacetylases
Denu, J. M. (2005) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2005.08.010 · Cited by 325 · see citing works
Of mice and men: the benefits of caloric restriction, exercise, and mimetics
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Calorie Restriction: Is AMPK a Key Sensor and Effector
Cantó, C., & Auwerx, J. (2011) · Physiology · doi:10.1152/physiol.00010.2011 · Cited by 282 · see citing works
Sirtuin catalysis and regulation
Feldman, J. L., Dittenhafer-Reed, K. E., & Denu, J. M. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.r112.378877 · Cited by 248 · see citing works
Crosstalk between poly(ADP-ribose) polymerase and sirtuin enzymes
Cantó, C., Sauve, A. A., & Bai, P. (2013) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2013.01.004 · Cited by 246 · see citing works
Neurotherapeutic applications of nanoparticles in Alzheimer’s disease
Sahni, J. K., Doggui, S., Ali, J., Baboota, S., Dao, L., & Ramassamy, C. (2011) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.11.033 · Cited by 219 · see citing works
Resveratrol as an active ingredient for cosmetic and dermatological applications: a review
Ratz-Łyko, A., & Arct, J. (2019) · Journal of Cosmetic and Laser Therapy · doi:10.1080/14764172.2018.1469767 · Cited by 216 · see citing works
Resveratrol as a calorie restriction mimetic: therapeutic implications
Chung, J. H., Manganiello, V., & Dyck, J. R. B. (2012) · Trends in Cell Biology · doi:10.1016/j.tcb.2012.07.004 · Cited by 192 · see citing works
NAD <sup>+</sup> metabolism: A therapeutic target for age-related metabolic disease
Mouchiroud, L., Houtkooper, R. H., & Auwerx, J. (2013) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2013.789479 · Cited by 193 · see citing works
“, 2004), although this is controversial (Bass et al., 2007; Kaeberlein et al., 2005).”
BackgroundGao, Z., Zhang, J., Kheterpal, I., Kennedy, N., Davis, R. J., & Ye, J. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.228874 · Cited by 187 · see citing works
Histone deacetylase 11 is a fatty-acid deacylase
Kutil, Z., Novakova, Z., Meleshin, M., Mikesova, J., Schutkowski, M., & Barinka, C. (2018) · ACS Chemical Biology · doi:10.1021/acschembio.7b00942 · Cited by 174 · see citing works
Role of SIRT1 and FOXO factors in eNOS transcriptional activation by resveratrol
Xia, N., Strand, S., Schlufter, F., Siuda, D., Reifenberg, G., Kleinert, H., Förstermann, U., & Li, H. (2013) · Nitric Oxide · doi:10.1016/j.niox.2013.04.001 · Cited by 157 · see citing works
Turn up the power - pharmacological activation of mitochondrial biogenesis in mouse models
Komen, J. C., & Thorburn, D. R. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12413 · Cited by 149 · see citing works
Histone deacetylase 11 is an ε-N-Myristoyllysine hydrolase
Moreno-Yruela, C., Galleano, I., Madsen, A. S., & Olsen, C. A. (2018) · Cell Chemical Biology · doi:10.1016/j.chembiol.2018.04.007 · Cited by 149 · see citing works
Dietary restriction.; mitochondrial function and aging: From yeast to humans
Ruetenik, A., & Barrientos, A. (2015) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2015.05.005 · Cited by 139 · see citing works
Alcaín, F. J., & Villalba, J. M. (2009) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543770902762893 · Cited by 137 · see citing works
Drugs that modulate aging: the promising yet difficult path ahead
Kennedy, B. K., & Pennypacker, J. K. (2014) · Translational research · doi:10.1016/j.trsl.2013.11.007 · Cited by 127 · see citing works
Self-citationMetabolic effects of resveratrol: Addressing the controversies
Bitterman, J. L., & Chung, J. H. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1808-8 · Cited by 109 · see citing works
Resveratrol: Challenges in Translation to the Clinic — A Critical Discussion
Subramanian, L., Youssef, S., Bhattacharya, S., Kenealey, J., Polans, A. S., & van Ginkel, P. R. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-1486 · Cited by 103 · see citing works
Delipidating effect of resveratrol metabolites in 3<scp>T</scp>3‐<scp>L</scp>1 adipocytes
Lasa, A., Churruca, I., Eseberri, I., Andrés‐Lacueva, C., & Portillo, M. P. (2012) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201100772 · Cited by 103 · see citing works
Biala, A., Tauriainen, E., Siltanen, A., Shi, J., Merasto, S., Louhelainen, M., Martonen, E., Finckenberg, P., Muller, D. N., & Mervaala, E. (2010) · Blood Pressure · doi:10.3109/08037051.2010.481808 · Cited by 97 · see citing works
Bao, J., & Sack, M. N. (2010) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-010-0402-y · Cited by 67 · see citing works
Sirtuins, nuclear hormone receptor acetylation and transcriptional regulation
Whittle, J. R., Powell, M. J., Popov, V. M., Shirley, L. A., Wang, C., & Pestell, R. G. (2007) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2007.07.007 · Cited by 51 · see citing works
Circadian Redox and Metabolic Oscillations in Mammalian Systems
O'Neill, J. S., & Feeney, K. A. (2014) · Antioxidants & Redox Signaling · doi:10.1089/ars.2013.5582 · Cited by 51 · see citing works
Revelations into resveratrol's mechanism
(2012) · Nature Medicine · doi:10.1038/nm.2727 · Cited by 17 · see citing works
Alive and well? Exploring disease by studying lifespan
Brett, J. O., & Rando, T. A. (2014) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2014.05.004 · Cited by 12 · see citing works
Toro, T. B., Bryant, J. R., & Watt, T. J. (2017) · Biochemistry · doi:10.1021/acs.biochem.7b00270 · Cited by 11 · see citing works
- 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.
- ORCID
- 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
- hybrid
- doi.org
- Licence
- 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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