Franklin H. Epstein Lecture: Sirtuins, aging, and medicine.

In this year's Franklin H. Epstein Lecture, Leonard Guarente summarizes the many biologic properties of the sirtuin family of deacetylases and explains why enhancement or inhibition of specific sirtuins may influence many common diseases and longevity.

[1]  L. Nogowski,et al.  Resveratrol and genistein as adenosine triphosphate-depleting agents in fat cells. , 2011, Metabolism: clinical and experimental.

[2]  F. Villarroya,et al.  Sirt1 acts in association with PPARα to protect the heart from hypertrophy, metabolic dysregulation, and inflammation. , 2011, Cardiovascular research.

[3]  L. Guarente,et al.  Sirtuins at a glance , 2011, Journal of Cell Science.

[4]  P. Pandolfi,et al.  SIRT3 opposes reprogramming of cancer cell metabolism through HIF1α destabilization. , 2011, Cancer cell.

[5]  Byoung Kil Lee,et al.  Expression of DBC1 and SIRT1 is associated with poor prognosis for breast carcinoma. , 2011, Human pathology.

[6]  De-Pei Liu,et al.  SIRT1 inhibits angiotensin II-induced vascular smooth muscle cell hypertrophy. , 2011, Acta biochimica et biophysica Sinica.

[7]  L. Guarente,et al.  SirT3 suppresses hypoxia inducible factor 1α and tumor growth by inhibiting mitochondrial ROS production , 2011, Oncogene.

[8]  Lloyd M. Smith,et al.  Sirt3 promotes the urea cycle and fatty acid oxidation during dietary restriction. , 2011, Molecular cell.

[9]  S. Park,et al.  Sirt3-mediated deacetylation of evolutionarily conserved lysine 122 regulates MnSOD activity in response to stress. , 2010, Molecular cell.

[10]  Danica Chen,et al.  Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation. , 2010, Cell metabolism.

[11]  Wei Yu,et al.  Sirt3 Mediates Reduction of Oxidative Damage and Prevention of Age-Related Hearing Loss under Caloric Restriction , 2010, Cell.

[12]  V. Haroutunian,et al.  Acetylation of Tau Inhibits Its Degradation and Contributes to Tauopathy , 2010, Neuron.

[13]  C. Deng,et al.  Liver Steatosis and Increased ChREBP Expression in Mice Carrying a Liver Specific SIRT1 Null Mutation under a Normal Feeding Condition , 2010, International journal of biological sciences.

[14]  H. Horvitz,et al.  3-Ketoacyl thiolase delays aging of Caenorhabditis elegans and is required for lifespan extension mediated by sir-2.1 , 2010, Proceedings of the National Academy of Sciences.

[15]  T. Veenstra,et al.  SIRT1 Deacetylates and Inhibits SREBP-1C Activity in Regulation of Hepatic Lipid Metabolism* , 2010, The Journal of Biological Chemistry.

[16]  David P. Carney,et al.  SIRT1 Activation by Small Molecules , 2010, The Journal of Biological Chemistry.

[17]  Olivia Baré,et al.  SIRT4 Regulates Fatty Acid Oxidation and Mitochondrial Gene Expression in Liver and Muscle Cells , 2010, The Journal of Biological Chemistry.

[18]  D. Holtzman,et al.  SIRT1 Promotes the Central Adaptive Response to Diet Restriction through Activation of the Dorsomedial and Lateral Nuclei of the Hypothalamus , 2010, The Journal of Neuroscience.

[19]  Lois E. H. Smith,et al.  SIRT1 Is Essential for Normal Cognitive Function and Synaptic Plasticity , 2010, The Journal of Neuroscience.

[20]  R. Coppari,et al.  SIRT1 deacetylase in POMC neurons is required for homeostatic defenses against diet-induced obesity. , 2010, Cell metabolism.

[21]  P. Puigserver,et al.  Conserved role of SIRT1 orthologs in fasting-dependent inhibition of the lipid/cholesterol regulator SREBP. , 2010, Genes & development.

[22]  L. Guarente,et al.  RETRACTED: SIRT1 Suppresses β-Amyloid Production by Activating the α-Secretase Gene ADAM10 , 2010, Cell.

[23]  L. Tsai,et al.  A novel pathway regulates memory and plasticity via SIRT1 and miR-134 , 2010, Nature.

[24]  F. Mulero,et al.  Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer. , 2010, Nature communications.

[25]  L. Guarente,et al.  Aging and disease: connections to sirtuins , 2010, Aging cell.

[26]  T. Uzu,et al.  Calorie restriction enhances cell adaptation to hypoxia through Sirt1-dependent mitochondrial autophagy in mouse aged kidney. , 2010, The Journal of clinical investigation.

[27]  R. Harris,et al.  Sirt1 activation protects the mouse renal medulla from oxidative injury. , 2010, The Journal of clinical investigation.

[28]  N. Ruderman,et al.  AMPK and SIRT1: a long-standing partnership? , 2010, American journal of physiology. Endocrinology and metabolism.

[29]  N. Inagaki,et al.  Overexpression of SIRT5 confirms its involvement in deacetylation and activation of carbamoyl phosphate synthetase 1. , 2010, Biochemical and biophysical research communications.

[30]  K. Skorecki,et al.  Kidney-specific Overexpression of Sirt1 Protects against Acute Kidney Injury by Retaining Peroxisome Function , 2010, The Journal of Biological Chemistry.

[31]  G. Gores,et al.  Deleted in breast cancer-1 regulates SIRT1 activity and contributes to high-fat diet-induced liver steatosis in mice. , 2010, The Journal of clinical investigation.

[32]  C. Deng,et al.  SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stress. , 2010, Cancer cell.

[33]  D. Sinclair,et al.  Mammalian sirtuins: biological insights and disease relevance. , 2010, Annual review of pathology.

[34]  Venkataraman Thanabal,et al.  SRT1720, SRT2183, SRT1460, and Resveratrol Are Not Direct Activators of SIRT1♦ , 2010, The Journal of Biological Chemistry.

[35]  Diana Wang,et al.  SIRT1 Suppresses b-Amyloid Production by Activating the a-Secretase Gene ADAM10 , 2010 .

[36]  Robert V Farese,et al.  SIRT 3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation , 2010 .

[37]  T. Veenstra,et al.  FXR acetylation is normally dynamically regulated by p300 and SIRT1 but constitutively elevated in metabolic disease states. , 2009, Cell metabolism.

[38]  Gene Kim,et al.  Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice. , 2009, The Journal of clinical investigation.

[39]  M. McBurney,et al.  SirT1-null mice develop tumors at normal rates but are poorly protected by resveratrol , 2009, Oncogene.

[40]  Takashi Nakagawa,et al.  SIRT5 Deacetylates Carbamoyl Phosphate Synthetase 1 and Regulates the Urea Cycle , 2009, Cell.

[41]  Qing Xu,et al.  Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation. , 2009, Cell metabolism.

[42]  G. Remuzzi,et al.  Disruption of the Ang II type 1 receptor promotes longevity in mice. , 2009, The Journal of clinical investigation.

[43]  Corby K. Martin,et al.  Caloric restriction alone and with exercise improves CVD risk in healthy non-obese individuals. , 2009, Atherosclerosis.

[44]  J. M. Villalba,et al.  Sirtuin inhibitors , 2009, Expert opinion on therapeutic patents.

[45]  Howard Y. Chang,et al.  SIRT6 Links Histone H3 Lysine 9 Deacetylation to NF-κB-Dependent Gene Expression and Organismal Life Span , 2009, Cell.

[46]  S. Schinner.  AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity , 2009 .

[47]  David J. Gagne,et al.  Small molecule activators of SIRT1 replicate signaling pathways triggered by calorie restriction in vivo , 2009, BMC Syst. Biol..

[48]  C. Deng,et al.  Interplay among BRCA1, SIRT1, and Survivin during BRCA1-associated tumorigenesis. , 2008, Molecular cell.

[49]  Alexander S Banks,et al.  SirT1 gain of function increases energy efficiency and prevents diabetes in mice. , 2008, Cell metabolism.

[50]  Shiwei Song,et al.  A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis , 2008, Proceedings of the National Academy of Sciences.

[51]  J. Yates,et al.  A Fasting Inducible Switch Modulates Gluconeogenesis Via Activator-Coactivator Exchange , 2008, Nature.

[52]  Y. Ouchi,et al.  Cilostazol Inhibits Oxidative Stress–Induced Premature Senescence Via Upregulation of Sirt1 in Human Endothelial Cells , 2008, Arteriosclerosis, thrombosis, and vascular biology.

[53]  Paolo Sassone-Corsi,et al.  The NAD+-Dependent Deacetylase SIRT1 Modulates CLOCK-Mediated Chromatin Remodeling and Circadian Control , 2008, Cell.

[54]  Florian Kreppel,et al.  SIRT1 Regulates Circadian Clock Gene Expression through PER2 Deacetylation , 2008, Cell.

[55]  P. Pfluger,et al.  Sirt1 protects against high-fat diet-induced metabolic damage , 2008, Proceedings of the National Academy of Sciences.

[56]  F. Alt,et al.  Tissue-specific regulation of SIRT1 by calorie restriction. , 2008, Genes & development.

[57]  K. Sunagawa,et al.  SIRT1, a Longevity Gene, Downregulates Angiotensin II Type 1 Receptor Expression in Vascular Smooth Muscle Cells , 2008, Arteriosclerosis, thrombosis, and vascular biology.

[58]  D. Allison,et al.  A Low Dose of Dietary Resveratrol Partially Mimics Caloric Restriction and Retards Aging Parameters in Mice , 2008, PloS one.

[59]  W. Hahn,et al.  The SIRT1 Deacetylase Suppresses Intestinal Tumorigenesis and Colon Cancer Growth , 2008, PloS one.

[60]  J. Denu,et al.  The Sirtuin family: therapeutic targets to treat diseases of aging. , 2008, Current opinion in chemical biology.

[61]  J. Qin,et al.  Negative regulation of the deacetylase SIRT1 by DBC1 , 2008, Nature.

[62]  Junjie Chen,et al.  DBC1 is a negative regulator of SIRT1 , 2008, Nature.

[63]  L. Guarente.  Mitochondria—A Nexus for Aging, Calorie Restriction, and Sirtuins? , 2008, Cell.

[64]  F. Alt,et al.  Tissue-specific regulation of SIRT 1 by calorie restriction , 2008 .

[65]  Andrew D. Steele,et al.  SIRT1 transgenic mice show phenotypes resembling calorie restriction , 2007, Aging cell.

[66]  Amy V. Lynch,et al.  Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes , 2007, Nature.

[67]  L. Guarente,et al.  SIRT1 deacetylates and positively regulates the nuclear receptor LXR. , 2007, Molecular cell.

[68]  Eric Verdin,et al.  Mammalian Sir2 Homolog SIRT3 Regulates Global Mitochondrial Lysine Acetylation , 2007, Molecular and Cellular Biology.

[69]  Andre Fischer,et al.  SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis , 2007, The EMBO journal.

[70]  D. Selkoe,et al.  Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide , 2007, Nature Reviews Molecular Cell Biology.

[71]  G. Passarino,et al.  Characterization of a bidirectional promoter shared between two human genes related to aging: SIRT3 and PSMD13. , 2007, Genomics.

[72]  P. Puigserver,et al.  Resveratrol Improves Mitochondrial Function and Protects against Metabolic Disease by Activating SIRT1 and PGC-1α , 2006, Cell.

[73]  P. Puigserver,et al.  Resveratrol improves health and survival of mice on a high-calorie diet , 2006, Nature.

[74]  F. Alt,et al.  SIRT4 Inhibits Glutamate Dehydrogenase and Opposes the Effects of Calorie Restriction in Pancreatic β Cells , 2006, Cell.

[75]  Jun Wang,et al.  Neuronal SIRT1 Activation as a Novel Mechanism Underlying the Prevention of Alzheimer Disease Amyloid Neuropathology by Calorie Restriction* , 2006, Journal of Biological Chemistry.

[76]  S. Baylin,et al.  Tumor Suppressor HIC1 Directly Regulates SIRT1 to Modulate p53-Dependent DNA-Damage Responses , 2005, Cell.

[77]  Emilio Clementi,et al.  Calorie Restriction Promotes Mitochondrial Biogenesis by Inducing the Expression of eNOS , 2005, Science.

[78]  S. Fields,et al.  Substrate-specific Activation of Sirtuins by Resveratrol* , 2005, Journal of Biological Chemistry.

[79]  Steven P Gygi,et al.  Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. , 2005, Nature.

[80]  B. Rogina,et al.  Sir2 mediates longevity in the fly through a pathway related to calorie restriction. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[81]  Namjin Chung,et al.  Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-γ , 2004, Nature.

[82]  M. Mayo,et al.  Modulation of NF‐κB‐dependent transcription and cell survival by the SIRT1 deacetylase , 2004, The EMBO journal.

[83]  Steven P. Gygi,et al.  Stress-Dependent Regulation of FOXO Transcription Factors by the SIRT1 Deacetylase , 2004, Science.

[84]  Delin Chen,et al.  Mammalian SIRT1 Represses Forkhead Transcription Factors , 2004, Cell.

[85]  A. Yashin,et al.  Variability of the SIRT3 gene, human silent information regulator Sir2 homologue, and survivorship in the elderly , 2003, Experimental Gerontology.

[86]  Phuong Chung,et al.  Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan , 2003, Nature.

[87]  L. Guarente,et al.  Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans , 2001, Nature.

[88]  Jianbiao Zheng,et al.  Inhibition of mitochondrial proton F0F1‐ATPase/ATP synthase by polyphenolic phytochemicals , 2000, British journal of pharmacology.

[89]  L. Guarente,et al.  Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase , 2000, Nature.

[90]  M. McVey,et al.  The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. , 1999, Genes & development.

[91]  L. Guarente,et al.  Extrachromosomal rDNA Circles— A Cause of Aging in Yeast , 1997, Cell.

[92]  Mala Murthy,et al.  Redistribution of Silencing Proteins from Telomeres to the Nucleolus Is Associated with Extension of Life Span in S. cerevisiae , 1997, Cell.