Oxidative Stress in Aging (eBook)

Preface 6
Table of Contents 8
Contributors 12
Section I: Introduction 16
Chapter 1 17
Introduction 17
1 Living in the Presence of Oxygen 17
1.1 History of Free Radical Theory from Lavoisier to Harman 18
1.2 Development and Derivatives of Free Radical Theory 19
1.2.1 Aging 20
2 Oxidative Stress in Aging: Format of the Book 20
Section I. Introduction 21
Section II. Role of Oxidative Stress in Aging 22
Part II-A Different Model Systems 22
Part II-B Comparative Approach 22
Section III. Oxidative Stress in Human Aging and Diseases 22
Section IV. Future 23
References 23
Chapter 2 25
The Basics of Oxidative Biochemistry 25
1 Chemistry of Reactive Oxygen Species 25
1.1 Superoxide 25
1.2 Hydrogen Peroxide 27
1.3 Hydroxyl Radical 27
2 Antioxidant System 27
2.1 SOD Accelerates Dismutation of Superoxide Radical 28
2.2 Peroxiredoxins are Major Scavengers of Endogenously Produced H2O2 29
2.3 How Many Unknown Antioxidant Genes are out There? 30
2.3.1 Biliverdin/Bilirubin and Biliverdin Reductase 31
2.3.2 Apolipoprotein D (ApoD) 31
2.3.3 Sulfiredoxin and Sestrin 31
2.4 ROS Sources 32
2.5 Measuring Oxidative Damage 34
2.5.1 Lipid Peroxidation 35
2.5.2 DNA Oxidative Damage 36
2.5.3 Protein Oxidation 37
2.6 How Does Oxidative Damage Kill or Compromise the Function of the Cell? 38
2.6.1 Lipid Peroxidation 38
2.6.2 DNA Oxidative Damage 39
2.6.3 Oxidative Damage to Proteins 40
3 Conclusions 40
References 40
Section II: The Role of Oxidative Stress in Aging 51
Part II-A: Different Model Systems 51
Chapter 3 53
Retrograde Response, Oxidative Stress, and Cellular Senescence 53
1 Introduction 53
2 Role of Mitochondrial ROS in Telomere-Dependent Senescence 54
3 Is Retrograde Signaling Part of a Senescence Signature? Does It Have a Causal Role? 56
4 Conclusions 63
References 64
Chapter 4 67
Reactive Oxygen Species in Molecular Pathways Controlling Aging in the Filamentous Fungus Podospora anserina 67
1 Introduction: Senescence in Podospora anserina 67
2 Mitochondrial DNA Instabilities 70
3 Oxidative Stress 71
3.1 ROS Generation 71
3.2 ROS Scavenging 73
Untitled 68
4 Retrograde Response 73
5 Mitochondrial Dynamics 74
6 Age-Related Changes in Cytoplasmic Copper Levels 75
7 ROS-Induced Apoptosis 75
8 Conclusions and Outlook 75
References 77
Chapter 5 81
Oxidative Stress and Aging in the Budding Yeast Saccharomyces cerevisiae 81
1 The Model System 81
2 ROS and Aging: A Lesson from Knockouts 83
3 More Than Just Damage 87
4 Age-Dependent Oxidative Damage Is Regulated 89
5 Conclusions 90
References 91
Chapter 6 95
Oxidative Stress and Aging in the Nematode Caenorhabditis elegans 95
1 Introduction 95
2 Why Test Theories of Aging in C. elegans? 97
2.1 C. elegans as a Model for Studies of Aging 97
2.2 Approaches to Testing Oxidation-Related Theories of Aging 98
3 Is Aging in C. elegans Caused by Molecular Damage? 99
3.1 Age Increases in Damage to Protein, DNA, and Lipid 99
3.2 Age Increases in Blue Fluorescence 99
3.3 Molecular Damage in Mutants with Altered Life Span 101
3.4 Conclusions 101
4 Do Reactive Oxygen Species Cause Aging in C. elegans? 101
4.1 Alterations of Prooxidant Levels 101
4.2 Does Elevated ROS Accelerate Age Changes in Molecular Damage? 103
4.3 Antioxidant Defense and Aging 103
4.4 SOD and Catalase 104
4.5 Other Antioxidant Defenses 106
4.6 Noncatalytic Antioxidants 108
4.7 Conclusions 109
5 Do Mitochondria Play a Role in C. elegans Aging? 109
5.1 Does Superoxide Production by Mitochondria Contribute to Aging? 109
5.2 Mitochondria, Superoxide, and Aging in C. elegans 110
5.3 Mitochondrial ETC Defects Can Increase or Reduce Life Span 110
5.4 Is Superoxide Production Important for Mitochondrial Effects on Aging? 113
5.5 Uncoupling Proteins and Aging in C. elegans 114
5.6 Conclusions 114
6 Is Metabolic Rate a Determinant of Aging in C. elegans? 115
6.1 Metabolic Rate and Superoxide Production 115
6.2 Effects of Temperature on Life Span 115
6.3 Metabolic Rate in Long-Lived Nematodes 115
6.4 Differences in Energy Metabolism between C. elegans and Vertebrates 116
6.5 Conclusions 117
7 Overall Conclusions 117
References 118
Chapter 7 125
Roles of Oxidative Stress in the Aging Process of Drosophila melanogaster 125
1 Introduction 125
1.1 The Free Radical/Oxidative Stress Hypothesis of Aging 125
1.2 Interpretation of Experimental Tests of the Oxidative Stress Hypothesis 126
2 Physiological Adaptation 128
2.1 The Rate-of-Living Hypothesis 129
2.2 Departures from the Rate-of-Living Model 129
2.3 Ramifications for Longevity Studies in Poikilotherms 130
2.4 Ramifications for the Oxidative Stress Hypothesis 131
3 Experimental Manipulations of Oxidant Production 132
3.1 Mitochondrial Catalase 132
3.2 Uncoupling Proteins (UCPs) 133
3.3 Iron Metabolism 134
3.4 Cytochrome c Oxidase (COX) 134
4 Overexpression of Antioxidants 135
4.1 Nonenzymatic Antioxidants 135
4.2 Enzymatic Antioxidants 135
5 Repair 136
5.1 Methionine Sulfoxide Reductase 137
5.2 Protein Carboxyl Methyltransferase (PCMT) 137
5.3 Small Heat Shock Proteins (Hsp22) 137
6 Conclusions (Perspective) 138
References 139
Chapter 8 143
Does Oxidative Stress Limit Mouse Life Span? 143
1 Introduction 144
2 The Model: Mus musculus “laboratorienscis” 145
3 Life Span of Antioxidant and Oxidative Damage Repair Knockout Mice 146
3.1 Sod1-/- or CuZnSOD Knockout 146
3.2 MnSOD Knockout 147
3.3 Sod3-/-/EC-SOD Knockout 149
3.4 Glutathione Peroxidase-1 Knockout 149
3.5 Peroxiredoxin Knockout 150
3.6 MsrA Knockout 151
3.7 Knockouts of the Ogg1/Myh 8-oxo-dG Control System 151
3.8 Combinations of Antioxidant Knockouts 152
3.9 Gene Expression Changes in Antioxidant Knockout Mice: An Independent Measure of In Vivo Oxidative Stress and Compensatory Antioxidant Up-Regulation 152
4 Conclusions 153
References 154
Part II-B: The Comparative Approach 162
Chapter 9 163
Mitochondrial Free Radical Production and Caloric Restriction: Implications in Vertebrate Longevity and Aging 163
1 Introduction 163
2 Mitochondrial ROS Generation Rate: Comparative Studies 164
3 Mitochondrial DNA Oxidative Damage: Comparative Studies 167
4 Caloric Restriction, Mitochondrial ROS Production, DNA Oxidative Damage, and Longevity 168
5 Protein Restriction, Methionine Restriction and Longevity 170
6 Protein Restriction, Methionine Restriction, mtROS Production, and Oxidative Damage 170
References 172
Section III: Oxidative Stress in Human Aging and Diseases 177
Chapter 10 179
Deregulation of Mitochondrial Function: A Potential Common Theme for Cardiovascular Disease Development 179
1 Introduction 179
2 Atherogenesis 180
2.1 Changing Concepts of Atherogenesis 182
2.2 Mechanisms of CVD 182
3 Mitochondrial Paradigm for CVD Development 183
3.1 Mitochondria and Their DNA 183
3.2 Mitochondrial Oxidative Phosphorylation 184
3.3 Mitochondrial Oxidant Production and Regulation 186
3.4 Mitochondrial Damage and Function 187
4 CVD Risk Factors and Mitochondrial Damage 189
5 Mitochondrial Function and Genetics May Influence Disease Susceptibility 191
6 Conclusions 194
References 194
Chapter 11 205
Oxidative Stress in Type 2 Diabetes Mellitus 205
1 Introduction 205
2 Normal Glucose Tolerance 206
3 Pathophysiology of T2DM 206
3.1 Insulin Resistance 207
4 The Insulin Receptor 208
5 Insulin Receptor Signal Transduction 208
6 Molecular Mechanism of Insulin Resistance 209
7 Reactive Oxygen Species (ROS) and Insulin Action 210
7.1 Possible Role of Oxidative Stress in Pathogenesis of Insulin Resistance 210
7.2 Molecular Mechanism of Oxidative Stress-Induced Insulin Resistance 211
7.3 beta Cell Failure 212
7.4 Cellular Mechanisms of b Cell Failure and Role of ROS 214
7.5 Molecular Etiology of Type 2 Diabetic Complications 216
8 Summary and Conclusions 219
References 219
Chapter 12 227
DNA Oxidative Damage and Cancer 227
1 Introduction 227
2 Oxygen, Reactive Oxygen, and Cancer 228
3 ROS-Mediated DNA Damage 230
4 8-OxodG and Cancer 230
5 DNA Base Excision Repair and Cancer 233
6 Mitochondria, ROS, and Cancer 235
7 Conclusions 238
References 238
Chapter 13 243
Oxidative Stress in Hypertension 243
1 Introduction 243
2 Linking Oxidative Stress with Hypertension 244
3 NAD(P)H Oxidase: A Major Prooxidant Enzyme 247
3.1 Nox Isoforms 247
3.1.1 Nox1 247
3.1.2 Nox2 248
3.1.3 Nox4 249
3.2 p22phox 249
3.3 p47phox 250
3.4 p67phox 250
3.5 Rac1 251
4 Superoxide Dismutases, Glutathione Peroxidases, and Catalase: Predominant Antioxidant Defense Systems 251
4.1 Superoxide Dismutases 251
4.1.1 CuZnSOD 252
4.1.2 MnSOD 253
4.1.3 EC-SOD 254
4.2 Glutathione Peroxidases 255
4.3 Catalase 255
5 Summary 256
References 257
Chapter 14 267
Aging and Cardiac Ischemia-Mitochondria and Free Radical Considerations 267
1 Cardiac Mitochondria and Metabolism 267
2 Cardiac Mitochondrial Generation of Reactive Oxygen Species (ROS) 268
3 Pathologic Mechanisms in Ischemia-Reperfusion (IR) Injury 270
4 Changes in Risk Factors and Underlying Causes of IR Injury during Aging 272
5 Changes in Cardiac Mitochondria during Aging 273
5.1 Aging and Complex III 273
5.2 Aging and Complex IV 274
6 Response of Cardiac Mitochondria to IR Injury: Changes during Aging 275
7 Efficacy of Cardioprotection in Aging 276
8 Concluding Remarks 277
References 277
Chapter 15 283
Role of the Antioxidant Network in the Prevention of Age-Related Diseases 283
1 Introduction 283
2 Galenic Antioxidant Supplementations and Disease Prevention 285
2.1 Cardiovascular Diseases 285
2.2 Cancer 286
2.3 Evidence from Meta-Analysis 287
3 Nonenzymatic Antioxidant Network 288
4 Measurement of Total Antioxidant Capacity In Vivo 289
4.1 Single Electron Transfer Assays 290
4.1.1 FRAP Assay 290
4.1.2 TEAC Assay 290
4.2 Hydrogen Atom Transfer Assays 290
4.2.1 TRAP Assay 290
4.2.2 Fluo-Lip Assay 291
4.2.3 ORAC Assay 291
5 Dietary Modulation of the Antioxidant Network 292
6 Imbalance of Nonenzymatic Antioxidant Network and Degenerative Diseases 295
7 Conclusions 298
References 299
Section IV: Future 305
Chapter 16 307
Reactive Oxygen Species as Signaling Molecules 307
1 Reactive Oxygen Species (ROS) in Growth Factor Signaling 307
2 NADPH Oxidases 309
3 Protein Tyrosine Phosphatases 311
4 Mitochondrial ROS 313
5 ROS in Cellular Senescence 315
6 ROS and Stem Cells 318
7 Summary 319
References 319
Chapter 17 323
Summary and Outlook 323
1 Does Oxidative Stress Limit Life Span? 323
2 Role of Oxidative Stress in Pathology 325
3 Epilogue 326
Index 327