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Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan
Abstract
In diverse organisms, calorie restriction slows the pace of ageing and increases maximum lifespan. In the budding yeast Saccharomyces cerevisiae, calorie restriction extends lifespan by increasing the activity of Sir2 (ref. 1), a member of the conserved sirtuin family of NAD(+)-dependent protein deacetylases. Included in this family are SIR-2.1, a Caenorhabditis elegans enzyme that regulates lifespan, and SIRT1, a human deacetylase that promotes cell survival by negatively regulating the p53 tumour suppressor. Here we report the discovery of three classes of small molecules that activate sirtuins. We show that the potent activator resveratrol, a polyphenol found in red wine, lowers the Michaelis constant of SIRT1 for both the acetylated substrate and NAD(+), and increases cell survival by stimulating SIRT1-dependent deacetylation of p53. In yeast, resveratrol mimics calorie restriction by stimulating Sir2, increasing DNA stability and extending lifespan by 70%. We discuss possible evolutionary origins of this phenomenon and suggest new lines of research into the therapeutic use of sirtuin activators.
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In the citing paper
“Resveratrol, a natural polyphenolic compound present in various dietary components such as mulberries, peanuts, grapes and red wine, was identified as the most potent activator of SIRT1 (Howitz et al., 2003).”
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 Howitz et al., 2003
In the citing paper
“Experiments in animal models have shown that resveratrol significantly reduces body weight [14].”
From The Role of Resveratrol Administration in Human Obesity (2021) · cites this paper as [14]
In the citing paper
“SIRT-1 is a human deacetylase that negatively regulates the p53 tumor suppressor gene, thus it promotes cell survival [14].”
From The Role of Resveratrol Administration in Human Obesity (2021) · cites this paper as [14]
In the citing paper
“an intervention capable of extending life span in many different organisms from yeast to mammals (Cohen et al., 2004; Howitz et al., 2003; Lin et al., 2000; Rogina and Helfand, 2004; Wood et al., 2004”
From DNA Repair, Genome Stability, and Aging (2005) · cites this paper as Howitz et al., 2003
In the citing paper
“resveratrol, a plant polyphenol commonly found in red wine that extends lifespan in yeast, worms and flies [143, 144].”
From PGC-1α in aging and anti-aging interventions (2009) · cites this paper as [143]
In the citing paper
“Indeed, this polyphenol has been reported to activate the AMPK and SIRT1 (Howitz et al., 2003; Hawley et al., 2010)”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Howitz et al., 2003
In the citing paper
“Resveratrol prolongs the life of flies (Bauer et al., 2004), worms (Baur and Sinclair, 2006), and the replicative lifespan of yeast (Howitz et al., 2003), but not yeast’s chronological lifespan (our unpublished observations).”
From The Search for Antiaging Interventions: From Elixirs to Fasting Regimens (2014) · cites this paper as Howitz et al., 2003
In the citing paper
“Resveratrol, an ingredient in red wines, is a polyphenolic SIRT1 activator that, like calorie restriction, has anti-aging effects in lower organisms (22, 143, 331), reduces signs of aging in mice (248), and extends survival (22).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [143]
Citations
Cites
ON THE NATURE OF ALLOSTERIC TRANSITIONS: A PLAUSIBLE MODEL.
Monod, J., Wyman, J., & Changeux, J. (1965) · Journal of Molecular Biology · doi:10.1016/s0022-2836(65)80285-6 · Cited by 7,681
Cancer chemopreventive activity of resveratrol, a natural product derived from grapes
Jang, M., Cai, L., Udeani, G. O., Slowing, K. V., Thomas, C. F., Beecher, C. W. W., Fong, H. H. S., Farnsworth, N. R., Kinghorn, A. D., Mehta, R. G., et al. (1997) · Science · doi:10.1126/science.275.5297.218 · Cited by 4,935 · cited 1×
“The most potent activator was resveratrol (3,5,4′-trihydroxystilbene), a polyphenol found in red wine that is associated with a surprising number of health benefits, most notably the mitigation of age-related diseases, including neurodegeneration, carcinogenesis and atherosclerosi”
BackgroundMiddleton, E., Kandaswami, C., & Theoharides, T. C. (2000) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01472-8 · Cited by 4,882
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
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 2,690
Kaeberlein, M., McVey, M., & Guarente, L. (1999) · Genes & Development · doi:10.1101/gad.13.19.2570 · Cited by 2,253 · cited 1×
“Together, these findings add to the body of evidence that yeast ageing is caused by genomic instabilit”
BackgroundNegative 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
Lin, S.-J., Defossez, P.-A., & Guarente, L. (2000) · Science · doi:10.1126/science.289.5487.2126 · Cited by 1,775
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 1,603
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
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Items 301–400 of 1,038
Csiszár, A., Smith, K. E., Labinskyy, N., Orosz, Z. Z., Rivera, A., & Ungvari, Z. I. (2006) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00340.2006 · Cited by 275
Zelber‐Sagi, S., Salomone, F., & Mlynarsky, L. (2017) · Liver International · doi:10.1111/liv.13435 · Cited by 273
The Sirtuin family: therapeutic targets to treat diseases of aging
Milne, J. C., & Denu, J. M. (2008) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2008.01.019 · Cited by 274
Sirtuins in Epigenetic Regulation
Jing, H., & Lin, H. (2015) · Chemical Reviews · doi:10.1021/cr500457h · Cited by 276
Hodawadekar, S. C., & Marmorstein, R. (2007) · Oncogene · doi:10.1038/sj.onc.1210619 · Cited by 292
Chuang, C., & McIntosh, M. (2011) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-072610-145149 · Cited by 277
Youn, H. S., Lee, J. Y., Fitzgerald, K. A., Young, H. A., Akira, S., & Hwang, D. H. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.5.3339 · Cited by 270
Dietary resveratrol prevents Alzheimer’s markers and increases life span in SAMP8
Porquet, D., Casadesús, G., Bayod, S., Vicente, A., Canudas, A. M., Vilaplana, J., Pelegrı́, C., Sanfeliu, C., Camins, A., Pallàs, M., et al. (2012) · AGE · doi:10.1007/s11357-012-9489-4 · Cited by 272
High-Yield Resveratrol Production in Engineered Escherichia coli
Lim, C. G., Fowler, Z. L., Hueller, T., Schaffer, S., & Koffas, M. A. G. (2011) · Applied and Environmental Microbiology · doi:10.1128/aem.02186-10 · Cited by 269
Ralston, L., Subramanian, S., Matsuno, M., & Yu, O. S. (2005) · PLANT PHYSIOLOGY · doi:10.1104/pp.104.054502 · Cited by 267
Resveratrol: Preventing properties against vascular alterations and ageing
Delmas, D., Jannin, B., & Latruffe, N. (2005) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.200400098 · Cited by 277
Brookins-Danz, E. D., Skramsted, J., Henry, N., Bennett, J. A., & Keller, R. S. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.03.011 · Cited by 273
Dose-Dependency of Resveratrol in Providing Health Benefits
Mukherjee, S., Dudley, J. I., & Das, D. K. (2010) · Dose-Response · doi:10.2203/dose-response.09-015.mukherjee · Cited by 266
Pallos, J., Bodai, L., Lukácsovich, T., Purcell, J. M., Steffan, J. S., Thompson, L. M., & Marsh, J. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn273 · Cited by 272
Baxter, R. A. (2008) · Journal of Cosmetic Dermatology · doi:10.1111/j.1473-2165.2008.00354.x · Cited by 265
Functions of the sirtuin deacylase SIRT5 in normal physiology and pathobiology
Kumar, S., & Lombard, D. B. (2018) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2018.1458071 · Cited by 273
Overlapping and distinct functions for a Caenorhabditis elegans SIR2 and DAF-16/FOXO
Wang, Y., & Tissenbaum, H. A. (2005) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2005.09.005 · Cited by 269
Structural basis for allosteric, substrate-dependent stimulation of SIRT1 activity by resveratrolPreprint
Cao, D., Wang, M., Qiu, X., Liu, D., Jiang, H., Yang, N., & Xu, R.-M. (2015) · Genes & Development · doi:10.1101/gad.265462.115 · Cited by 268
Epigenetics of Aging and Aging-related Disease
Brunet, A., & Berger, S. L. (2014) · The Journals of Gerontology Series A · doi:10.1093/gerona/glu042 · Cited by 268
Structural Basis of Inhibition of the Human NAD+-Dependent Deacetylase SIRT5 by Suramin
Schuetz, A., Min, J., Antoshenko, T., Wang, C.-L., Allali‐Hassani, A., Dong, A., Loppnau, P., Vedadi, M., Bochkarev, A. V., Sternglanz, R., et al. (2007) · Structure · doi:10.1016/j.str.2007.02.002 · Cited by 267
Snyder, S. A., Breazzano, S. P., Ross, A. G., Lin, Y., & Zografos, A. L. (2009) · Journal of the American Chemical Society · doi:10.1021/ja806183r · Cited by 261
Nicotinamide-induced Mitophagy
Jang, S., Kang, H. T., & Hwang, E. S. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.363747 · Cited by 264
Hano, C., & Tungmunnithum, D. (2020) · Medicines · doi:10.3390/medicines7050026 · Cited by 275
Resveratrol and derivatives for the prevention and treatment of cancer
Fulda, S. (2010) · Drug Discovery Today · doi:10.1016/j.drudis.2010.07.005 · Cited by 266
Salermide, a Sirtuin inhibitor with a strong cancer-specific proapoptotic effect
Lara, E., Mai, A., Calvanese, V., Altucci, L., López‐Nieva, P., Martínez‐Chantar, M. L., Varela‐Rey, M., Rotili, D., Nebbioso, A., Ropero, S., et al. (2008) · Oncogene · doi:10.1038/onc.2008.436 · Cited by 267
Role of AMPK mediated pathways in autophagy and aging
Ge, Y., Zhou, M., Chen, C., Wu, X., & Wang, X. (2021) · Biochimie · doi:10.1016/j.biochi.2021.11.008 · Cited by 262
Kobori, M., Masumoto, S., Akimoto, Y., & Oike, H. (2010) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201000392 · Cited by 264
SIRT1: recent lessons from mouse models
Herranz, D., & Serrano, M. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2962 · Cited by 261
Activation of Sirt1 by Resveratrol Inhibits TNF-α Induced Inflammation in Fibroblasts
Zhu, X., Liu, Q., Wang, M., Liang, M., Yang, X., Xu, X., Zou, H., & Qiu, J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0027081 · Cited by 259
Human trials exploring anti-aging medicines
Guarente, L., Sinclair, D. A., & Kroemer, G. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2023.12.007 · Cited by 266
Self-citationPourtau, N., Jennings, R., Pelzer, E., Pallas, J. A., & Wingler, A. (2006) · Planta · doi:10.1007/s00425-006-0243-y · Cited by 255
Austin, M. B., Bowman, M. E., Ferrer, J.-L., Schröder, J., & Noel, J. P. (2004) · Chemistry & Biology · doi:10.1016/j.chembiol.2004.05.024 · Cited by 253
Nielsen, J. (2017) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-061516-044757 · Cited by 252
Han, J., Pan, X., Xu, Y., Xiao, Y., An, Y., Tie, L., Pan, Y., & Li, X. (2012) · Autophagy · doi:10.4161/auto.19471 · Cited by 256
Virgili, F., & Marino, M. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.08.001 · Cited by 249
Chemical probes for histone-modifying enzymes
Cole, P. A. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.111 · Cited by 253
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
Global heterochromatin loss: a unifying theory of aging?
Tsurumi, A., & Li, W. (2012) · Epigenetics · doi:10.4161/epi.20540 · Cited by 256
Liu, D., Gharavi, R. B., PITTA, M. G. R., Gleichmann, M., & Mattson, M. P. (2009) · NeuroMolecular Medicine · doi:10.1007/s12017-009-8058-1 · Cited by 257
Ageing and neurodegenerative diseases
Hung, C.-W., Chen, Y., Hsieh, W.-L., Chiou, S., & Kao, C.-L. (2010) · Ageing Research Reviews · doi:10.1016/j.arr.2010.08.006 · Cited by 257
Structural basis for sirtuin function: What we know and what we don't
Sanders, B. D., Jackson, B. A., & Marmorstein, R. (2009) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2009.09.009 · Cited by 254
Resveratrol supplementation: Where are we now and where should we go?
Novelle, M. G., Wahl, D., Diéguez, C., Bernier, M., & de Cabo, R. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.01.002 · Cited by 254
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
Ferretta, A., Gaballo, A., Tanzarella, P., Piccoli, C., Capitanio, N., Nico, B., Annese, T., Paola, M. D., Dell’Aquila, C., Mari, M. D., et al. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.02.010 · Cited by 243
AMP-activated protein kinase, stress responses and cardiovascular diseases
Wang, S., Song, P., & Zou, M. (2012) · Clinical Science · doi:10.1042/cs20110625 · Cited by 251
Skeletal muscle mitochondria as a target to prevent or treat type 2 diabetes mellitus
Hesselink, M. K. C., Schrauwen-Hinderling, V., & Schrauwen, P. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.104 · Cited by 242
Berghe, W. V. (2012) · Pharmacological Research · doi:10.1016/j.phrs.2012.03.007 · Cited by 245
Uittenbogaard, M. N., & Chiaramello, A. (2014) · Current Pharmaceutical Design · doi:10.2174/1381612820666140305224906 · Cited by 246
Cisplatin-induced Kidney Dysfunction and Perspectives on Improving Treatment Strategies
Oh, G., Kim, H., Shen, A., Lee, S. B., Khadka, D., Pandit, A., & So, H. (2014) · Electrolytes & Blood Pressure · doi:10.5049/ebp.2014.12.2.55 · Cited by 240
Gillette, T. G., & Hill, J. A. (2015) · Circulation Research · doi:10.1161/circresaha.116.303630 · Cited by 260
Phenolic fortification of yogurt using grape and callus extracts
Karaaslan, M., Özden, M., Vardın, H., & Türkoğlu, H. (2010) · LWT · doi:10.1016/j.lwt.2010.12.009 · Cited by 241
Jiménez, Y., Mattison, J. A., Pearson, K. J., Martín‐Montalvo, A., Palacios, H. H., Sossong, A. M., Ward, T. M., Younts, C. M., Lewis, K. N., Allard, J. S., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.09.004 · Cited by 247
Sorting out functions of sirtuins in cancer
Roth, M., & Chen, W. (2013) · Oncogene · doi:10.1038/onc.2013.120 · Cited by 242
Resveratrol Mimics Ischemic Preconditioning in the Brain
Raval, A. P., Dave, K. R., & Pérez‐Pinzón, M. A. (2006) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600262 · Cited by 239
Biological actions and molecular effects of resveratrol, pterostilbene, and 3′-hydroxypterostilbene
Tsai, H.-Y., Ho, C., & Chen, Y. (2016) · Journal of Food and Drug Analysis · doi:10.1016/j.jfda.2016.07.004 · Cited by 242
Resveratrol increases vascular oxidative stress resistance
Ungvari, Z. I., Orosz, Z. Z., Rivera, A., Labinskyy, N., Xiangmin, Z., Olson, S. C., Podlutsky, A. J., & Csiszár, A. (2007) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01258.2006 · Cited by 243
Pasinetti, G. M., Wang, J., Ho, L., Zhao, W., & Dubner, L. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.10.006 · Cited by 244
Ghanim, H., Sia, C. L., Abuaysheh, S., Korzeniewski, K., Patnaik, P., Marumganti, A., Chaudhuri, A., & Dandona, P. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-0482 · Cited by 241
Crystal Structure of Quinone Reductase 2 in Complex with Resveratrol ,
Buryanovskyy, L., Fu, Y., Boyd, M., Ma, Y., Hsieh, T., WU, J. M., & Zhang, Z. (2004) · Biochemistry · doi:10.1021/bi049162o · Cited by 242
Sirtuin regulation in aging and injury
Poulose, N., & Raju, R. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.08.017 · Cited by 236
Maher, P. A., Dargusch, R., Bodai, L., Gerard, P. E., Purcell, J. M., & Marsh, J. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq460 · Cited by 239
Lee, H., Zhang, P., Herrmann, A., Yang, C., Xin, H., Wang, Z., Hoon, D. S. �., Forman, S. J., Jove, R., Riggs, A. D., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1205132109 · Cited by 241
Radical medicine: treating ageing to cure disease
Finkel, T. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1763 · Cited by 234
Bauer, J. H., Goupil, S., Garber, G. B., & Helfand, S. L. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0403493101 · Cited by 234
Harikumar, K. B., Kunnumakkara, A. B., Sethi, G., Diagaradjane, P., Anand, P., Pandey, M. K., Gelovani, J. G., Krishnan, S., Guha, S., & Aggarwal, B. B. (2010) · International Journal of Cancer · doi:10.1002/ijc.25041 · Cited by 233
Resveratrol in cardiovascular health and disease
Petrovski, G., Gurusamy, N., & Das, D. K. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05843.x · Cited by 232
Smoliga, J. M., & Blanchard, O. L. (2014) · Molecules · doi:10.3390/molecules191117154 · Cited by 236
Effects of Resveratrol and SIRT1 on PGC-1α Activity and Mitochondrial Biogenesis: A Reevaluation
Higashida, K., Kim, S. H., Jung, S. R., Asaka, M., Holloszy, J. O., & Han, D.-H. (2013) · PLoS Biology · doi:10.1371/journal.pbio.1001603 · Cited by 237
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 232
Self-citationShakibaei, M., Buhrmann, C., & Mobasheri, A. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.198713 · Cited by 230
Martín, A. R., Villegas, I., Sánchéz‐Hidalgo, M., & Alarcón‐de‐la‐Lastra, C. (2006) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706469 · Cited by 231
Functional foods, herbs and nutraceuticals: towards biochemical mechanisms of healthy aging
Ferrari, C. K. B. (2004) · Biogerontology · doi:10.1007/s10522-004-2566-z · Cited by 227
HST2 Mediates SIR2 -Independent Life-Span Extension by Calorie Restriction
Lamming, D. W., Latorre‐Esteves, M., Medvedik, O., Wong, S. N., Tsang, F. A., Wang, C., Lin, S.-J., & Sinclair, D. A. (2005) · Science · doi:10.1126/science.1113611 · Cited by 227
Self-citationZhang, Y., & Rock, C. O. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403697200 · Cited by 227
Targeting immune dysfunction in aging
Borgoni, S., Kudryashova, K. S., Burka, K., & de Magalhães, J. P. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101410 · Cited by 232
Botanical Phenolics and Brain Health
Sun, A. Y., Wang, Q., Simonyi, Á., & Sun, G. Y. (2008) · NeuroMolecular Medicine · doi:10.1007/s12017-008-8052-z · Cited by 229
A protein deacetylase SIRT1 is a negative regulator of metalloproteinase‐9
Nakamaru, Y., Vuppusetty, C., Wada, H., Milne, J. C., Ito, M., Rossios, C., Elliot, M., Hogg, J. C., Kharitonov, S. A., Goto, H., et al. (2009) · The FASEB Journal · doi:10.1096/fj.08-125468 · Cited by 224
Hasan, M. M., & Bae, H. (2017) · Molecules · doi:10.3390/molecules22020294 · Cited by 224
Small-Molecule Allosteric Activators of Sirtuins
Sinclair, D. A., & Guarente, L. (2011) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010611-134657 · Cited by 226
Self-citationSafety studies conducted on high-purity trans-resveratrol in experimental animals
Williams, L. D., Burdock, G. A., Edwards, J. A., Beck, M., & Bausch, J. (2009) · Food and Chemical Toxicology · doi:10.1016/j.fct.2009.06.002 · Cited by 226
Naringenin, a citrus flavonoid, increases muscle cell glucose uptake via AMPK
Zygmunt, K., Faubert, B., MacNeil, J., & Tsiani, E. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.06.048 · Cited by 227
Molecular mechanism of endothelial and vascular aging: implications for cardiovascular disease
Camici, G. G., Savarese, G., Akhmedov, A., & Lüscher, T. F. (2015) · European Heart Journal · doi:10.1093/eurheartj/ehv587 · Cited by 226
Resveratrol, an Nrf2 activator, ameliorates aging-related progressive renal injury
Kim, E. N., Lim, J. H., Kim, M. Y., Ban, T. H., Jang, I.-A., Yoon, H. E., Park, C. W., Chang, Y. S., & Choi, B. S. (2018) · Aging · doi:10.18632/aging.101361 · Cited by 222
Sirtuin deacetylases in neurodegenerative diseases of aging
Herskovits, A. Z., & Guarente, L. (2013) · Cell Research · doi:10.1038/cr.2013.70 · Cited by 230
SIRT1: Regulation of longevity via autophagy
Salminen, A., & Kaarniranta, K. (2009) · Cellular Signalling · doi:10.1016/j.cellsig.2009.02.014 · Cited by 227
Maternal Obesity, Inflammation, and Developmental Programming
Segovia, S. A., Vickers, M. H., Gray, C. L., & Reynolds, C. M. (2014) · BioMed Research International · doi:10.1155/2014/418975 · Cited by 233
Metabolic engineering for plant natural product biosynthesis in microbes
Chemler, J. A., & Koffas, M. A. G. (2008) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2008.10.011 · Cited by 221
Therapeutic potential of resveratrol in Alzheimer's disease
Vingtdeux, V., Dreses‐Werringloer, U., Zhao, H., Davies, P. J., & Marambaud, P. (2008) · BMC Neuroscience · doi:10.1186/1471-2202-9-s2-s6 · Cited by 230
Maejima, Y., Adachi, S., Ito, H., Hirao, K., & Isobe, M. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00358.x · Cited by 223
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Metadata
- Authors
- 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., Scherer, B., & Sinclair, D. A.
- Affiliations
- Harvard University (US)
- Corresponding author
- Sinclair, David A.
- Venue
- Nature
- Published
- 2003-08-24
- Volume
- 425
- Issue
- 6954
- Pages
- 191-196
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2088381487
- Cited by
- 3,796
- References
- 30
- Citations by year
- 2026: 77 · 2025: 73 · 2024: 117 · 2023: 99 · 2022: 133 · 2021: 159 · 2020: 159 · 2019: 158 · 2018: 181 · 2017: 189 · 2016: 198 · 2015: 215 · 2014: 227 · 2013: 267 · 2012: 253
- FWCI
- 51.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institute on Aging (R37AG028730, P01AG027916, R01AG028730, R01AG019719, R01AG019972, R13AG033466)
- National Institute of General Medical Sciences (R01GM068072)
- 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 › Biochemical and Molecular Research
- Keywords
- sirtuins, Sir2, SIRT1, resveratrol, caloric restriction, lifespan extension, aging, Sir2p, p53 deacetylation, NAD+-dependent deacetylase, DNA stability, Saccharomyces cerevisiae, small molecule activators
- MeSH terms
- Resveratrol, Acetylation, Catalysis, Cell Line, Cell Survival, Flavonoids, Histone Deacetylases, Humans, Kinetics, Longevity, Phenols, Polymers, Recombination, Genetic, Saccharomyces cerevisiae, Stilbenes, Wine, Tumor Suppressor Protein p53, Cellular Senescence, Caloric Restriction, Sirtuins, Silent Information Regulator Proteins, Saccharomyces cerevisiae, Sirtuin 1, Sirtuin 2, Polyphenols
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