SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1
Open accessAbstract
Sirtuins catalyze NAD(+)-dependent protein deacetylation and are critical regulators of transcription, apoptosis, metabolism, and aging. There are seven human sirtuins (SIRT1-7), and SIRT1 has been implicated as a key mediator of the pathways downstream of calorie restriction that have been shown to delay the onset and reduce the incidence of age-related diseases such as type 2 diabetes. Increasing SIRT1 activity, either by transgenic overexpression of the Sirt1 gene in mice or by pharmacological activation by small molecule activators resveratrol and SRT1720, has shown beneficial effects in rodent models of type 2 diabetes, indicating that SIRT1 may represent an attractive therapeutic target. Herein, we have assessed purported SIRT1 activators by employing biochemical assays utilizing native substrates, including a p53-derived peptide substrate lacking a fluorophore as well as the purified native full-length protein substrates p53 and acetyl-CoA synthetase1. SRT1720, its structurally related compounds SRT2183 and SRT1460, and resveratrol do not lead to apparent activation of SIRT1 with native peptide or full-length protein substrates, whereas they do activate SIRT1 with peptide substrate containing a covalently attached fluorophore. Employing NMR, surface plasmon resonance, and isothermal calorimetry techniques, we provide evidence that these compounds directly interact with fluorophore-containing peptide substrates. Furthermore, we demonstrate that SRT1720 neither lowers plasma glucose nor improves mitochondrial capacity in mice fed a high fat diet. SRT1720, SRT2183, SRT1460, and resveratrol exhibit multiple off-target activities against receptors, enzymes, transporters, and ion channels. Taken together, we conclude that SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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 Pacholec et al., 2010
Cites
Resveratrol improves health and survival of mice on a high-calorie diet
Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., Prabhu, V. V., Allard, J. S., Lopez-Lluch, G., Lewis, K., et al. (2006) · Nature · doi:10.1038/nature05354 · Cited by 4,290 · see citing works
Lagouge, M., Argmann, C., Gerhart-Hines, Z., Meziane, H., Lerin, C., Daussin, F., Messadeq, N., Milne, J., Lambert, P., Elliott, P., et al. (2006) · Cell · doi:10.1016/j.cell.2006.11.013 · Cited by 4,057 · see citing works
Enzyme kinetics; behavior and analysis of rapid equilibrium and steady state enzyme systems
(1994) · International Journal of Biochemistry · doi:10.1016/0020-711x(94)90021-3 · Cited by 2,978 · 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
Kaeberlein, M., McVey, M., & Guarente, L. (1999) · Genes & Development · doi:10.1101/gad.13.19.2570 · Cited by 2,253 · see citing works
Negative 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
Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase
Cohen, H. Y., Miller, C., Bitterman, K. J., Wall, N. R., Hekking, B., Kessler, B., Howitz, K. T., Gorospe, M., de Cabo, R., & Sinclair, D. A. (2004) · Science · doi:10.1126/science.1099196 · Cited by 1,924 · 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
Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes
Milne, J. C., Lambert, P. D., Schenk, S., Carney, D. P., Smith, J. J., Gagne, D. J., Jin, L., Boss, O., Perni, R. B., Vu, C. B., et al. (2007) · Nature · doi:10.1038/nature06261 · Cited by 1,707 · see citing works
Sir2 mediates longevity in the fly through a pathway related to calorie restriction
Rogina, B., & Helfand, S. L. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0404184101 · Cited by 1,361 · see citing works
Mechanism of Human SIRT1 Activation by Resveratrol
Borra, M. T., Smith, B. C., & Denu, J. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501250200 · Cited by 1,065 · see citing works
Human SIR2 deacetylates p53 and antagonizes PML/p53‐induced cellular senescence
Langley, E., Pearson, M., Faretta, M., Bauer, U., Frye, R. A., Minucci, S., Pelicci, P. G., & Kouzarides, T. (2002) · The EMBO Journal · doi:10.1093/emboj/21.10.2383 · Cited by 859 · see citing works
Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases
Hallows, W. C., Lee, S., & Denu, J. M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604392103 · Cited by 792 · see citing works
Calorie Restriction Increases Muscle Mitochondrial Biogenesis in Healthy Humans
Civitarese, A. E., Carling, S., Heilbronn, L. K., Hulver, M. H., Ukropcova, B., Deutsch, W. A., Smith, S. R., & Ravussin, E. (2007) · PLoS Medicine · doi:10.1371/journal.pmed.0040076 · Cited by 790 · 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
Substrate-specific activation of sirtuins by resveratrol
Kaeberlein, M., McDonagh, T., Heltweg, B., Hixon, J., Westman, E. A., Caldwell, S. D., Napper, A., Curtis, R., DiStefano, P. S., Fields, S., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500655200 · Cited by 745 · see citing works
The Establishment, Inheritance, and Function of Silenced Chromatin in Saccharomyces cerevisiae
Rusché, L. N., Kirchmaier, A. L., & Rine, J. (2003) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161547 · Cited by 726 · see citing works
Feige, J. N., Lagouge, M., Canto, C., Strehle, A., Houten, S. M., Milne, J. C., Lambert, P. D., Mataki, C., Elliott, P. J., & Auwerx, J. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.08.017 · Cited by 719 · 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
SirT1 Gain of Function Increases Energy Efficiency and Prevents Diabetes in Mice
Banks, A. S., Kon, N., Knight, C. M., Matsumoto, M., Juárez, R. G., Rossetti, L., Gu, W. J., & Accili, D. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.08.014 · Cited by 636 · see citing works
Moynihan, K. A., Grimm, A. A., Plueger, M. M., Bernal‐Mizrachi, E., Ford, E. L., CRAS-MÉNEUR, C. M. H., Permutt, M. A., & Imai, S. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.07.001 · Cited by 628 · see citing works
Insulin resistance as a predictor of age-related diseases
Facchini, F. S., Hua, N., Abbasi, F., & Reaven, G. M. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.8.7763 · Cited by 594 · see citing works
Sir2-dependent activation of acetyl-CoA synthetase by deacetylation of active lysine
Starai, V. J., Celic, I., Cole, R. N., Boeke, J. D., & Escalante-Semerena, J. C. (2002) · Science · doi:10.1126/science.1077650 · Cited by 564 · see citing works
Discovery of Indoles as Potent and Selective Inhibitors of the Deacetylase SIRT1
Napper, A. D., Hixon, J., McDonagh, T., Keavey, K., Pons, J., Barker, J., Yau, W. T., Amouzegh, P., Flegg, A., Hamelin, E. M.-N., et al. (2005) · Journal of Medicinal Chemistry · doi:10.1021/jm050522v · Cited by 524 · see citing works
Role for Human SIRT2 NAD-Dependent Deacetylase Activity in Control of Mitotic Exit in the Cell Cycle
Dryden, S. C., Nahhas, F. A., Nowak, J. E., Goustin, A. S., & Tainsky, M. A. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.9.3173-3185.2003 · Cited by 500 · 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
Liang, F.-X., Kume, S., & Koya, D. (2009) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2009.101 · Cited by 356 · see citing works
Sulaiman, M., Matta, M., Sunderesan, N. R., Gupta, M. P., Periasamy, M., & Gupta, M. P. (2009) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00418.2009 · Cited by 284 · see citing works
Caloric restriction reverses hepatic insulin resistance in aging rats by decreasing visceral fat.
Barzilai, N., Banerjee, S., Hawkins, M. A., Chen, W., & Rossetti, L. (1998) · Journal of Clinical Investigation · doi:10.1172/jci485 · Cited by 268 · see citing works
Luong, A., Hannah, V. C., Brown, M. S., & Goldstein, J. L. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m004160200 · Cited by 266 · see citing works
The molecular biology of the SIR proteins
Gasser, S. M., & Cockell, M. M. (2001) · Gene · doi:10.1016/s0378-1119(01)00741-7 · Cited by 263 · see citing works
Mechanism of Nicotinamide Inhibition and Transglycosidation by Sir2 Histone/Protein Deacetylases
Jackson, M. D., Schmidt, M. T., Oppenheimer, N. J., & Denu, J. M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306552200 · Cited by 238 · 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
Smith, J. J., Kenney, R. D., Gagne, D. J., Frushour, B. P., Ladd, W., Galonek, H. L., Israelian, K., Song, J. J., Razvadauskaite, G., Lynch, A. V., et al. (2009) · BMC Systems Biology · doi:10.1186/1752-0509-3-31 · Cited by 210 · see citing works
Gracia‐Sancho, J., Villarreal, G., Zhang, Y., & García‐Cardeña, G. (2009) · Cardiovascular Research · doi:10.1093/cvr/cvp337 · Cited by 176 · see citing works
Glucose Tolerance and Skeletal Muscle Gene Expression in Response to Alternate Day Fasting
Heilbronn, L. K., Civitarese, A. E., Bogacka, I., Smith, S. R., Hulver, M. W., & Ravussin, É. (2005) · Obesity Research · doi:10.1038/oby.2005.61 · Cited by 173 · see citing works
Yamazaki, Y., Usui, I., Kanatani, Y., Matsuya, Y., Tsuneyama, K., Fujisaka, S., Bukhari, A., Suzuki, H., Senda, S., Imanishi, S., et al. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90997.2008 · Cited by 164 · see citing works
Mechanisms and Molecular Probes of Sirtuins
Smith, B. C., Hallows, W. C., & Denu, J. M. (2008) · Chemistry & Biology · doi:10.1016/j.chembiol.2008.09.009 · Cited by 136 · see citing works
Central Administration of Resveratrol Improves Diet-Induced Diabetes
Ramadori, G., Gautron, L., Fujikawa, T., Vianna, C. R., Elmquist, J. K., & Coppari, R. (2009) · Endocrinology · doi:10.1210/en.2009-0528 · Cited by 125 · see citing works
Albani, D., Polito, L., & Forloni, G. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-1215 · Cited by 122 · see citing works
Identification and Characterization of a Novel p300-mediated p53 Acetylation Site, Lysine 305
Wang, Y.-H., Tsay, Y.-G., Tan, B. C.-M., Lo, W.-Y., & Lee, S.-C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212574200 · Cited by 92 · see citing works
Sir2 Deacetylases Exhibit Nucleophilic Participation of Acetyl-Lysine in NAD+ Cleavage
Smith, B. C., & Denu, J. M. (2007) · Journal of the American Chemical Society · doi:10.1021/ja070162w · Cited by 81 · see citing works
Sauve, A. A., & Schramm, V. L. (2004) · Current Medicinal Chemistry · doi:10.2174/0929867043455675 · Cited by 74 · see citing works
Sirtuins: a conserved key unlocking AceCS activity
North, B. J., & Sinclair, D. A. (2006) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2006.11.002 · Cited by 59 · see citing works
Dual role of Zn2+ in maintaining structural integrity and suppressing deacetylase activity of SIRT1
Chen, L., Yu, F., Zhou, Y., Zhu, W., Shen, X., Chen, K., Jiang, H., & Liu, D. (2009) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2009.10.021 · Cited by 32 · see citing works
Screening for positive allosteric modulators of biological targets
Groebe, D. R. (2006) · Drug Discovery Today · doi:10.1016/j.drudis.2006.05.010 · Cited by 21 · see citing works
Ishikawa, M., FUJINO, T., Sakashita, H., et al. (1995) · The Tohoku Journal of Experimental Medicine · doi:10.1620/tjem.175.55 · Cited by 15 · see citing works
Purification of Recombinant p53 from Sf9 Insect Cells
Sun, X. Z., Nguyen, J., & Momand, J. A. (2003) · Humana Press eBooks · doi:10.1385/1-59259-408-5:17 · Cited by 9 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The AMPK signalling pathway coordinates cell growth, autophagy and metabolism
Mihaylova, M. M., & Shaw, R. J. (2011) · Nature Cell Biology · doi:10.1038/ncb2329 · Cited by 2,923 · see citing works
Sirtuins as regulators of metabolism and healthspan
Houtkooper, R. H., Pirinen, E., & Auwerx, J. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3293 · Cited by 2,008 · see citing works
Cantó, C., Menzies, K. J., & Auwerx, J. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.023 · Cited by 1,648 · 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
NAD <sup>+</sup> in aging, metabolism, and neurodegeneration
Verdin, E. (2015) · Science · doi:10.1126/science.aac4854 · Cited by 1,319 · see citing works
Timmers, S., Konings, E., Bilet, L., Houtkooper, R. H., van de Weijer, T., Goossens, G. H., Hoeks, J., van der Krieken, S., Ryu, D., Kersten, S., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.10.002 · Cited by 1,320 · see citing works
Epigenetic protein families: a new frontier for drug discovery
Arrowsmith, C. H., Bountra, C., Fish, P. V., Lee, K., & Schapira, M. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3674 · Cited by 1,327 · 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
PARP-1 inhibition increases mitochondrial metabolism through SIRT1 activation
Bai, P., Cantó, C., Oudart, H., Brunyánszki, A., Cen, Y., Thomas, C., Yamamoto, H., Huber, A., Kiss, B., Houtkooper, R. H., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.03.004 · Cited by 837 · 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
The promise and peril of chemical probes
Arrowsmith, C. H., Audia, J. E., Austin, C., Baell, J., Bennett, J., Blagg, J., Bountra, C., Brennan, P. E., Brown, P. J., Bunnage, M. E., et al. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1867 · Cited by 839 · see citing works
Use of Cells Expressing γ Subunit Variants to Identify Diverse Mechanisms of AMPK Activation
Hawley, S. A., Ross, F. A., Chevtzoff, C., Green, K. A., Evans, A., Fogarty, S., Towler, M. C., Brown, L. J., Ogunbayo, O. A., Evans, A. M., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.04.001 · Cited by 773 · see citing works
Luen Tang, B. (2016) · Molecules and Cells · doi:10.14348/molcells.2016.2318 · Cited by 740 · see citing works
NAD+ homeostasis in health and disease
Katsyuba, E., Romani, M., Hofer, D., & Auwerx, J. (2020) · Nature Metabolism · doi:10.1038/s42255-019-0161-5 · Cited by 627 · see citing works
Absence 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
Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer
Herranz, D., Muñoz-Martin, M., Cañamero, M., Mulero, F., Martinez-Pastor, B., Fernandez-Capetillo, O., & Serrano, M. (2010) · Nature Communications · doi:10.1038/ncomms1001 · Cited by 612 · see citing works
Guarente, L. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1100831 · Cited by 510 · 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
“An opposing model to direct SIRT1/activator binding suggested that STACs produced complexes with the substrate fluorophore in solution, leading the authors of that study to conclude that STAC effects on cells and animals may be indirect (Pacholec et al., 2010).”
BackgroundResveratrol: French Paradox Revisited
Catalgol, B., Batirel, S., Taga, Y., & Ozer, N. K. (2012) · Frontiers in Pharmacology · doi:10.3389/fphar.2012.00141 · Cited by 449 · 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
Hormonal regulation of hepatic glucose production in health and disease
Lin, H. V., & Accili, D. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.06.003 · Cited by 429 · 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
AMP-activated protein kinase and its downstream transcriptional pathways
Cantó, C., & Auwerx, J. (2010) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-010-0454-z · Cited by 421 · 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
Pharmacological approaches to restore mitochondrial function
Andreux, P. A., Houtkooper, R. H., & Auwerx, J. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4023 · Cited by 383 · 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
Li, X. (2013) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gms108 · Cited by 360 · see citing works
Repairing mitochondrial dysfunction in disease
Sorrentino, V., Menzies, K. J., & Auwerx, J. (2018) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010716-104908 · Cited by 337 · see citing works
Flavonoid Apigenin Is an Inhibitor of the NAD+ase CD38
Escande, C., Nin, V., Price, N. L., Capellini, V., Gomes, A. P., Barbosa, M. T., O’Neil, L., White, T. A., Sinclair, D. A., & Chini, E. N. (2013) · Diabetes · doi:10.2337/db12-1139 · Cited by 332 · see citing works
Of mice and men: the benefits of caloric restriction, exercise, and mimetics
Mercken, E. M., Carboneau, B. A., Krzysik-Walker, S. M., & de Cabo, R. (2012) · Ageing Research Reviews · doi:10.1016/j.arr.2011.11.005 · Cited by 318 · see citing works
Pilot study of resveratrol in older adults with impaired glucose tolerance
Crandall, J. P., Oram, V., Trandafirescu, G., Reid, M., Kishore, P., Hawkins, M., Cohen, H. W., & Barzilai, N. (2012) · The Journals of Gerontology: Series A · doi:10.1093/gerona/glr235 · Cited by 281 · 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
Increased podocyte Sirtuin-1 function attenuates diabetic kidney injury
Hong, Q., Zhang, L., Das, B., Li, Z., Liu, B., Cai, G., Chen, X., Chuang, P. Y., He, J. C., & Lee, K. (2018) · Kidney International · doi:10.1016/j.kint.2017.12.008 · Cited by 222 · see citing works
Metabolic networks of longevity
Houtkooper, R. H., Williams, R. W., & Auwerx, J. (2010) · Cell · doi:10.1016/j.cell.2010.06.029 · Cited by 217 · see citing works
Protective effects and mechanisms of sirtuins in the nervous system
Zhang, F., Wang, S., Gan, L., Vosler, P. S., Gao, Y., Zigmond, M. J., & Chen, J. (2011) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2011.09.001 · Cited by 211 · 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
“…the ATP synthase complex in the oxidative phosphorylation (Zheng & Ramirez, 2000), it was hypothesized that the effects of resveratrol could be mediated by activation of the AMPK, rather than direct SIRT1 activation (Beher et al., 2009; Canto et al., 2010; Pacholec et al., 2010; Um et al., 2010).”
BackgroundAMP-activated protein kinase: Also regulated by ADP?
Hardie, D. G., Carling, D., & Gamblin, S. J. (2011) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2011.06.004 · Cited by 187 · see citing works
Gurd, B. J. (2011) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/h11-070 · Cited by 171 · see citing works
Resveratrol improves hepatic steatosis by inducing autophagy through the cAMP signaling pathway
Zhang, Y., Chen, M., Zhou, Y., Yi, L., Gao, Y., Ran, L., Chen, S., Zhang, T., Zhou, X., Zou, D., et al. (2015) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201500016 · Cited by 170 · 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
Genome-environment interactions that modulate aging: powerful targets for drug discovery
de Magalhães, J. P., Wuttke, D., Wood, S. H., Plank, M., & Vora, C. (2012) · Pharmacological Reviews · doi:10.1124/pr.110.004499 · Cited by 136 · see citing works
Food, Nutrigenomics, and Neurodegeneration—Neuroprotection by What You Eat!
Virmani, A., Pinto, L., Binienda, Z., & Ali, S. (2013) · Molecular Neurobiology · doi:10.1007/s12035-013-8498-3 · Cited by 137 · see citing works
Resveratrol and obesity: can resveratrol relieve metabolic disturbances?
de Ligt, M., Timmers, S., & Schrauwen, P. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.11.012 · Cited by 135 · see citing works
Lysine deacetylation in ischaemic preconditioning: the role of SIRT1
Nadtochiy, S. M., Redman, E., Rahman, I., & Brookes, P. S. (2011) · Cardiovascular Research · doi:10.1093/cvr/cvq287 · Cited by 130 · see citing works
Role and possible mechanisms of Sirt1 in depression
Lu, G., Li, J., Zhang, H., Zhao, X., Yan, L.-J., & Yang, X. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/8596903 · Cited by 106 · see citing works
Lan, F., Weikel, K., Cacicedo, J., & Ido, Y. (2017) · Nutrients · doi:10.3390/nu9070751 · Cited by 112 · see citing works
Metabolic 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
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
Fadini, G. P., Ceolotto, G., Pagnin, E., de Kreutzenberg, S., & Avogaro, A. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2010.00642.x · Cited by 97 · see citing works
Caloric restriction and exercise “mimetics”: ready for prime time
Handschin, C. (2016) · Pharmacological Research · doi:10.1016/j.phrs.2015.11.009 · Cited by 72 · 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
Rowlands, B. D., Klugmann, M., & Rae, C. D. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.13916 · Cited by 38 · see citing works
Protective effect of EX-527 against high-fat diet-induced diabetic nephropathy in Zucker rats
Kundu, A., Richa, S., Dey, P., Kim, K. S., Son, J. Y., Kim, H. R., Lee, S.-Y., Lee, B.-H., Lee, K. Y., Kacew, S., et al. (2020) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2020.114899 · Cited by 27 · see citing works
- Authors
- Pacholec, M., Bleasdale, J. E., Chrunyk, B., Cunningham, D., Flynn, D., Garofalo, R. S., Griffith, D., Griffor, M., Loulakis, P., Pabst, B., Qiu, X., Stockman, B., Thanabal, V., Varghese, A., Ward, J., Withka, J., & Ahn, K.
- Affiliations
- Pfizer (United States) (US)
- Corresponding author
- Ahn, Kay
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2010-03
- Volume
- 285
- Issue
- 11
- Pages
- 8340-8351
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2832984
- OpenAlex
- W2157860216
- Cited by
- 915
- References
- 48
- Citations by year
- 2026: 31 · 2025: 22 · 2024: 20 · 2023: 19 · 2022: 31 · 2021: 42 · 2020: 55 · 2019: 36 · 2018: 37 · 2017: 40 · 2016: 65 · 2015: 69 · 2014: 74 · 2013: 80 · 2012: 99
- FWCI
- 49.03
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (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 › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Keywords
- SIRT1, sirtuin activators, SRT1720, resveratrol, p53, off-target effects, high-fat diet, type 2 diabetes, mitochondrial capacity, plasma glucose
- MeSH terms
- Resveratrol, Acetylation, Allosteric Regulation, Animals, Blood Glucose, Calorimetry, Diabetes Mellitus, Type 2, Dietary Fats, Enzyme Activation, Enzyme Inhibitors, Heterocyclic Compounds, 4 or More Rings, Humans, Mice, Obese, Rhodamines, Stilbenes, Substrate Specificity, Tumor Suppressor Protein p53, Nuclear Magnetic Resonance, Biomolecular, Surface Plasmon Resonance, Mice, Sirtuin 1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review