The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
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?
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
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Items 501–600 of 1,038
Jannin, B., Menzel, M., Berlot, J., Delmas, D., Lançon, A., & Latruffe, N. (2004) · Biochemical Pharmacology · doi:10.1016/j.bcp.2004.04.028 · Cited by 175
Resveratrol and novel potent activators of SIRT1: effects on aging and age-related diseases
Knutson, M. D., & Leeuwenburgh, C. (2008) · Nutrition Reviews · doi:10.1111/j.1753-4887.2008.00109.x · Cited by 178
Palikaras, K., Daskalaki, I., Markaki, M., & Tavernarakis, N. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.04.005 · Cited by 181
Kampkötter, A., Nkwonkam, C. G., Zurawski, R. F., Timpel, C., Chovolou, Y., Wätjen, W., & Kahl, R. (2007) · Toxicology · doi:10.1016/j.tox.2007.02.006 · Cited by 176
The journey of resveratrol from yeast to human
Timmers, S., Auwerx, J. H., & Schrauwen, P. (2012) · Aging · doi:10.18632/aging.100445 · Cited by 180
Ding, S., Jiang, J., Zhang, G., Bu, Y., Zhang, G., & Zhao, X. (2017) · PLoS ONE · doi:10.1371/journal.pone.0183541 · Cited by 175
Waldman, M., Cohen, K., Yadin, D., Nudelman, V., Gorfil, D., Schwartzman, M. L., Kornwoski, R., Aravot, D. J., Abraham, N. G., Arad, M., et al. (2018) · Cardiovascular Diabetology · doi:10.1186/s12933-018-0754-4 · Cited by 175
Sirtuins and their Biological Relevance in Aging and Age-Related Diseases
Zhao, L., Cao, J., Hu, K., He, X., Dou, Y., Tong, T., & Han, L. (2020) · Aging and Disease · doi:10.14336/ad.2019.0820 · Cited by 178
Dietary resveratrol alters lipid metabolism-related gene expression of mice on an atherogenic diet
Ahn, J., Cho, I., Kim, S., Kwon, D., & Ha, T. (2008) · Journal of Hepatology · doi:10.1016/j.jhep.2008.08.012 · Cited by 173
Das, S., Mitrovsky, G., Vasanthi, H. R., & Das, D. K. (2014) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2014/345105 · Cited by 173
RetractedSIRT1 Activation Confers Neuroprotection in Experimental Optic Neuritis
Shindler, K. S., Ventura, E. S., Rex, T. S., Elliott, P. J., & Rostami, A. M. (2007) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.07-0131 · Cited by 174
Rotchés-Ribalta, M., Andrés‐Lacueva, C., Estruch, R., Escribano, E., & Urpí-Sardà, M. (2012) · Pharmacological Research · doi:10.1016/j.phrs.2012.08.001 · Cited by 177
Resveratrol modulates murine collagen-induced arthritis by inhibiting Th17 and B-cell function
Xuzhu, G., Komai‐Koma, M., Leung, B. P. L., Howe, H. S., McSharry, C. P., McInnes, I. B., & Xu, D. (2011) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2011.149831 · Cited by 173
Total Synthesis of Resveratrol‐Based Natural Products: A Chemoselective Solution
Snyder, S. A., Zografos, A. L., & Lin, Y. (2007) · Angewandte Chemie International Edition · doi:10.1002/anie.200703333 · Cited by 173
Renal Protective Effects of Resveratrol
Kitada, M., & Koya, D. (2013) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2013/568093 · Cited by 174
Bevilacqua, L., Ramsey, J. J., Hagopian, K., Weindruch, R., & Harper, M.-E. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00435.2004 · Cited by 172
Venturelli, S., Berger, A., Böcker, A., Busch, C., Weiland, T., Noor, S., Leischner, C., Schleicher, S., Mayer, M., Weiß, T. S., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0073097 · Cited by 174
Porcu, M., & Chiarugi, A. (2004) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2004.12.009 · Cited by 172
Gurd, B. J. (2011) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/h11-070 · Cited by 171
The Role of Mammalian Sirtuins in the Regulation of Metabolism, Aging, and Longevity
Satoh, A., Stein, L. R., & Imai, S. (2011) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-21631-2_7 · Cited by 175
The Role of Oxidative Stress in the Pathogenesis??of COPD
Rahman, I. (2005) · Treatments in Respiratory Medicine · doi:10.2165/00151829-200504030-00003 · Cited by 171
Suter, M., Chen, A., Burdine, M., Choudhury, M., Harris, R. A., Lane, R. H., Friedman, J. E., Grove, K. L., Tackett, A. J., & Aagaard, K. M. (2012) · The FASEB Journal · doi:10.1096/fj.12-212878 · Cited by 175
Yun, H., Park, S., Kim, M., Yang, W. K., Im, D. U., Yang, K. R., Hong, J., Choe, W., Kang, I., Kim, S. S., et al. (2014) · FEBS Journal · doi:10.1111/febs.12949 · Cited by 177
Plant Hormesis Management with Biostimulants of Biotic Origin in Agriculture
Vargas-Hernández, M., Macias-Bobadilla, I., Guevara-González, R. G., Romero‐Gómez, S. D. J., Rico-García, E., Ocampo-Velazquez, R. V., Alvarez-Arquieta, L. D. L., & Torres‐Pacheco, I. (2017) · Frontiers in Plant Science · doi:10.3389/fpls.2017.01762 · Cited by 179
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
NAD metabolism and sirtuins: Metabolic regulation of protein deacetylation in stress and toxicity
Yang, T., & Sauve, A. A. (2006) · The AAPS Journal · doi:10.1208/aapsj080472 · Cited by 170
Phytochemicals and their impact on adipose tissue inflammation and diabetes
Leiherer, A., Muendlein, A., & Drexel, H. (2012) · Vascular Pharmacology · doi:10.1016/j.vph.2012.09.002 · Cited by 172
Neurodegenerative processes in Huntington's disease
Bano, D., Zanetti, F., Mende, Y., & Nicotera, P. (2011) · Cell Death and Disease · doi:10.1038/cddis.2011.112 · Cited by 173
Santos, A. L., Sinha, S., & Lindner, A. B. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/1941285 · Cited by 168
Mai, A., Massa, S., Lavu, S., Pezzi, R., Simeoni, S., Ragno, R., Mariotti, F. R., Chiani, F., Camilloni, G., & Sinclair, D. A. (2005) · Journal of Medicinal Chemistry · doi:10.1021/jm050100l · Cited by 173
Self-citationRecent Advances in the Study on Resveratrol
Nakata, R., Takahashi, S., & Inoue, H. (2012) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.35.273 · Cited by 171
Gallic Acid Regulates Body Weight and Glucose Homeostasis Through AMPK Activation
Doan, K. V., Ko, C. M., Kinyua, A. W., Yang, D. J., Choi, Y., Oh, I. Y., Nguyen, N. M., Ko, A., Choi, J. W., Jeong, Y., et al. (2014) · Endocrinology · doi:10.1210/en.2014-1354 · Cited by 171
SIRT1 stimulation by polyphenols is affected by their stability and metabolism
de Boer, V. C. J., de Goffau, M. C., Arts, I. C. W., Hollman, P. C. H., & Keijer, J. (2006) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.02.007 · Cited by 168
SIRT1 as a potential therapeutic target for treatment of nonalcoholic fatty liver disease
Çolak, Y., Öztürk, O., Şenateş, E., Tuncer, İ., Yorulmaz, E., Adalı, G., Doğanay, H. L., & Enc, F. Y. (2011) · Medical Science Monitor · doi:10.12659/msm.881749 · Cited by 168
Lançon, A., Delma, D., Osman‐Ponchet, H., Thenot, J. P., & Latruffe, N. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.02.164 · Cited by 167
A therapeutic role for sirtuins in diseases of aging?
Westphal, C. H., Dipp, M., & Guarente, L. (2007) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2007.09.008 · Cited by 168
Investigating the ADP-ribosyltransferase Activity of Sirtuins with NAD Analogues and 32 P-NAD
Du, J., Jiang, H. X., & Lin, H. (2009) · Biochemistry · doi:10.1021/bi802093g · Cited by 171
Resveratrol and Endothelial Nitric Oxide
Xia, N., Förstermann, U., & Li, H. (2014) · Molecules · doi:10.3390/molecules191016102 · Cited by 170
Cancer Chemoprevention by Targeting the Epigenome
Huang, P.-H., Plass, C., & Gerhäuser, C. (2011) · Current Drug Targets · doi:10.2174/138945011798184155 · Cited by 168
Birrell, M. A., McCluskie, K., Wong, S., Donnelly, L., Barnes, P. J., & Belvisi, M. G. (2005) · The FASEB Journal · doi:10.1096/fj.04-2691fje · Cited by 171
Resveratrol: Twenty Years of Growth, Development and Controversy
Pezzuto, J. M. (2018) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2018.176 · Cited by 173
Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances
Jiang, Q., Liu, J., Huang, S., Wang, X.-Y., Chen, X., Liu, G.-H., Ye, K., Song, W., Masters, C. L., Wang, J., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02145-7 · Cited by 165
Kubota, S., Kurihara, T., Mochimaru, H., Satofuka, S., Noda, K., Ozawa, Y., Oike, Y., Ishida, S., & Tsubota, K. (2009) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.08-2666 · Cited by 168
Dietary approaches that delay age-related diseases
Everitt, A. V., Hilmer, S. N., Brand-Miller, J. C., Jamieson, H. A., Truswell, A. S., Sharma, A. P., Mason, R. S., Morris, B. J., & Couteur, D. G. L. (2006) · Clinical Interventions in Aging · doi:10.2147/ciia.2006.1.1.11 · Cited by 168
Vetterli, L., Brun, T., Giovannoni, L., Bosco, D., & Maechler, P. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.176842 · Cited by 170
Guan, G., Chen, Y., & Dong, Y. (2025) · Antioxidants · doi:10.3390/antiox14010070 · Cited by 175
Ramis, M. R., Esteban, S., Miralles, A., Tan, D., & Reiter, R. J. (2015) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2015.03.008 · Cited by 165
Resveratrol and Ophthalmic Diseases
Abu‐Amero, K. K., Kondkar, A. A., & Chalam, K. V. (2016) · Nutrients · doi:10.3390/nu8040200 · Cited by 166
Mechanisms of Lifespan Regulation by Calorie Restriction and Intermittent Fasting in Model Organisms
Hwangbo, D., Lee, H., Abozaid, L. S., & Min, K. (2020) · Nutrients · doi:10.3390/nu12041194 · Cited by 173
Gómez‐Zorita, S., Fernández‐Quintela, A., Macarulla, M. T., Aguirre, L., Hijona, E., Bujanda, L., Milagro, F. I., Martínez, J. A., & Portillo, M. P. (2011) · British Journal Of Nutrition · doi:10.1017/s0007114511002753 · Cited by 163
Tillu, D. V., Melemedjian, O. K., Asiedu, M. N., Qu, N., Felice, M. D., Dussor, G. O., & Price, T. J. (2012) · Molecular Pain · doi:10.1186/1744-8069-8-5 · Cited by 170
Hori, Y. S., Kuno, A., Hosoda, R., Tanno, M., Miura, T., Shimamoto, K., & Horio, Y. (2011) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.111.183210 · Cited by 169
PGC-1α in aging and anti-aging interventions
Anderson, R., & Prolla, T. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.04.005 · Cited by 162
Concurrent regulation of AMP-activated protein kinase and SIRT1 in mammalian cells
Suchankova, G., Nelson, L. E., Gerhart-Hines, Z., Kelly, M., Gauthier, M.-S., Saha, A. K., Ido, Y., Puigserver, P., & Ruderman, N. B. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.11.130 · Cited by 162
Calorie restriction mimetics: Can you have your cake and eat it, too?
Ingram, D. K., & Roth, G. S. (2014) · Ageing Research Reviews · doi:10.1016/j.arr.2014.11.005 · Cited by 164
Autophagy, polyphenols and healthy ageing
Pallauf, K., & Rimbach, G. H. (2012) · Ageing Research Reviews · doi:10.1016/j.arr.2012.03.008 · Cited by 167
Neuronal Sirt3 Protects against Excitotoxic Injury in Mouse Cortical Neuron Culture
Kim, S. H., Lu, H., & Alano, C. C. (2011) · PLoS ONE · doi:10.1371/journal.pone.0014731 · Cited by 164
Dietary phytochemicals as epigenetic modifiers in cancer: Promise and challenges
Shankar, E., Kanwal, R., Candamo, M., & Gupta, S. (2016) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2016.04.002 · Cited by 163
Epigenetic Regulatory Mechanisms Induced by Resveratrol
Fernandes, G., Silva, G., Pavan, A. R., Chiba, D. E., Chin, C. M., & dos Santos, J. L. (2017) · Nutrients · doi:10.3390/nu9111201 · Cited by 166
Gruber, J., Tang, S. Y., & Halliwell, B. B. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1395.059 · Cited by 167
Sauve, A. A. (2010) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2010.01.021 · Cited by 165
Morita, Y., Wada‐Hiraike, O., Yano, T., Shirane, A., Hirano, M., Hiraike, H., Koyama, S., Oishi, H., Yoshino, O., Miyamoto, Y., et al. (2012) · Reproductive Biology and Endocrinology · doi:10.1186/1477-7827-10-14 · Cited by 165
Chu, F., Chou, P. M., Zheng, X. S., Mirkin, B. L., & Rebbaa, A. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-2002 · Cited by 162
Resveratrol and life extension
Agarwal, B., & Baur, J. A. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05850.x · Cited by 163
Structural Basis for Sirtuin Activity and Inhibition
Yuan, H., & Marmorstein, R. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.r112.372300 · Cited by 167
Plant phenolics as functional food ingredients
Santos‐Buelga, C., Gonzaléz‐Paramás, A. M., Taofiq, O., Ayuda‐Durán, B., & González‐Manzano, S. (2019) · Advances in food and nutrition research · doi:10.1016/bs.afnr.2019.02.012 · Cited by 165
Necdin Regulates p53 Acetylation via Sirtuin1 to Modulate DNA Damage Response in Cortical Neurons
Hasegawa, K., & Yoshikawa, K. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.3052-08.2008 · Cited by 162
Natural Compounds Modulating Mitochondrial Functions
Gibellini, L., Bianchini, E., Biasi, S. D., Nasi, M., Cossarizza, A., & Pinti, M. (2015) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2015/527209 · Cited by 159
Bai, L., Pang, W.-J., Yang, Y., & Yang, G.-S. (2007) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-007-9592-5 · Cited by 158
Epigenetic linkage of aging, cancer and nutrition
Daniel, M. G., & Tollefsbol, T. O. (2015) · Journal of Experimental Biology · doi:10.1242/jeb.107110 · Cited by 161
Design of aging intervention studies: the NIA interventions testing program
Nadon, N. L., Strong, R., Miller, R. A., Nelson, J., Javors, M., Sharp, Z. D., Peralba, J. M., & Harrison, D. E. (2008) · AGE · doi:10.1007/s11357-008-9048-1 · Cited by 142
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
SirT1 Is an Inhibitor of Proliferation and Tumor Formation in Colon Cancer
Kabra, N., Li, Z., Chen, L., Li, B., Zhang, X. M., Wang, C., Yeatman, T. J., Coppola, D., & Chen, J. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.000034 · Cited by 160
Resveratrol modulation of signal transduction in apoptosis and cell survival: A mini-review
Fulda, S., & Debatin, K. (2006) · Cancer Detection and Prevention · doi:10.1016/j.cdp.2006.03.007 · Cited by 158
Corpas, R., Griñán‐Ferré, C., Rodrı́guez-Farré, E., Pallàs, M., & Sanfeliu, C. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1157-y · Cited by 164
Zhang, G., Deng, Y.-J., Xie, Q.-Q., Ren, E., Ma, Z., He, X., Gao, Y., & Kang, X. (2020) · Clinica Chimica Acta · doi:10.1016/j.cca.2020.04.016 · Cited by 158
Immunosenescence: signaling pathways, diseases and therapeutic targets
Fu, Y., Wang, B., Alu, A., Hong, W., Hong, L., He, X., Shi, H., Cheng, P., & Yang, X. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02371-z · Cited by 168
Calorie restriction and SIR2 genes—Towards a mechanism
Guarente, L. (2005) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2005.03.013 · Cited by 160
Loren, D. J., Seeram, N. P., Schulman, R. N., & Holtzman, D. M. (2005) · Pediatric Research · doi:10.1203/01.pdr.0000157722.07810.15 · Cited by 157
Starvation response in mouse liver shows strong correlation with life-span-prolonging processes
Bauer, M. F., Hamm, A. C., Bonaus, M., Jacob, A., Jaekel, J., Schorle, H., Pankratz, M. J., & Katzenberger, J. D. (2004) · Physiological Genomics · doi:10.1152/physiolgenomics.00203.2003 · Cited by 157
He, X., Andersson, G., Lindgren, U., & Li, Y. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.09.053 · Cited by 156
Resveratrol is a class IA phosphoinositide 3-kinase inhibitor
Fröjdö, S., Cozzone, D., Vidal, H., & Pirola, L. (2007) · Biochemical Journal · doi:10.1042/bj20070236 · Cited by 158
Inhibition of mammalian S6 kinase by resveratrol suppresses autophagy
Armour, S. M., Baur, J. A., Hsieh, S. N., Land-Bracha, A., Thomas, S. Μ., & Sinclair, D. A. (2009) · Aging · doi:10.18632/aging.100056 · Cited by 160
Self-citationPomegranate Polyphenols and Resveratrol Protect the Neonatal Brain against Hypoxic-Ischemic Injury
West, T., Atzeva, M., & Holtzman, D. M. (2007) · Developmental Neuroscience · doi:10.1159/000105477 · Cited by 156
Dietary Manipulation of Histone Structure and Function
Delage, B., & Dashwood, R. H. (2008) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.28.061807.155354 · Cited by 160
The Role of Mitochondria in the Pathophysiology of Skeletal Muscle Insulin Resistance
Pagel-Langenickel, I., Bao, J., Pang, L., & Sack, M. N. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0003 · Cited by 154
Lee, J., Jo, D., Park, D., Chung, H. Y., & Mattson, M. P. (2014) · Pharmacological Reviews · doi:10.1124/pr.113.007757 · Cited by 155
Sirtuin Functions in Female Fertility: Possible Role in Oxidative Stress and Aging
Tatone, C., Emidio, G. D., Vitti, M., Carlo, M. D., Santini, S. J., D’Alessandro, A. M., Falone, S., & Amicarelli, F. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/659687 · Cited by 157
Trapp, J., Jochum, A., Meier, R., Saunders, L. R., Marshall, B. L., Kunick, C., Verdin, E. M., Goekjian, P. G., Sippl, W., & Jung, M. (2006) · Journal of Medicinal Chemistry · doi:10.1021/jm060118b · Cited by 153
The controversial world of sirtuins
Dang, W. (2012) · Drug Discovery Today Technologies · doi:10.1016/j.ddtec.2012.08.003 · Cited by 158
Sirt1: Role Under the Condition of Ischemia/Hypoxia
Meng, X., Tan, J., Li, M., Song, S., Miao, Y., & Zhang, Q. (2016) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-016-0355-2 · Cited by 153
Wu, P., Zhang, Z., Wang, F., & Chen, J. (2010) · Acta Pharmacologica Sinica · doi:10.1038/aps.2010.186 · Cited by 152
Funk, J. A., Odejinmi, S. I., & Schnellmann, R. G. (2010) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.109.161992 · Cited by 156
Apigenin-induced-apoptosis is mediated by the activation of PKCδ and caspases in leukemia cells
Vargo, M. A., Voss, O. H., Poustka, F., Cardounel, A. J., Grotewold, E., & Doseff, A. I. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2006.06.010 · Cited by 151
Sirtuin 1 (SIRT1): The Misunderstood HDAC
Stünkel, W., & Campbell, R. M. (2011) · SLAS DISCOVERY · doi:10.1177/1087057111422103 · Cited by 154
Xenohormetic and anti-aging activity of secoiridoid polyphenols present in extra virgin olive oil
Menéndez, J. A., Joven, J., Aragonès, G., Barrajón‐Catalán, E., Beltrán‐Debón, R., Borrás‐Linares, I., Camps, J., Corominas-Faja, B., Cufí, S., Fernández‐Arroyo, S., et al. (2013) · Cell Cycle · doi:10.4161/cc.23756 · Cited by 156
Endothelial mechanobiology in atherosclerosis
Wang, X., Shen, Y., Shang, M., Liu, X., & Munn, L. L. (2023) · Cardiovascular Research · doi:10.1093/cvr/cvad076 · Cited by 154
Nuts: Natural Pleiotropic Nutraceuticals
Ros, E., Singh, A., & O’Keefe, J. H. (2021) · Nutrients · doi:10.3390/nu13093269 · Cited by 155
Wang, K.-H., Lai, Y.-H., Chang, J., Ko, T.-F., Shyu, S., & Chiou, R. Y. ‐. (2004) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf048804b · Cited by 150
Neuronal protection by sirtuins in Alzheimer's disease
Anekonda, T. S., & Reddy, P. H. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03492.x · Cited by 152
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
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
