BOOK
Critical Reviews Oxidative Stress And Aging: Advances In Basic Science, Diagnostics And Intervention (In 2 Vols)
Cutler Richard G | Rodriguez Henry
(2002)
Additional Information
Book Details
Abstract
This innovative and comprehensive reference book provides the most up-to-date information pertaining to the translational research field of oxidative stress and aging. The book focuses on understanding the molecular basis of oxidative stress and its associated age-related diseases with the goal being the development of new and novel methods in treating the human aging processes. The book charts the course of this new and rapidly emerging field of Oxidative Stress Diagnostics and Therapeutics that will have a significant impact on the future economics, science and practice of medicine. Over 100 of the leading experts in this field whose specialty includes biogerontology, geriatric medicine, free radical chemistry and biology, oncology, cardiology, neurobiology, dermatology, pharmacology, nutrition, and molecular medicine, have contributed information to this book. This reference book is an essential reading material to a broad range of individuals including researchers, physicians, corporate industry leaders, graduate and medical school students, as well as the many health conscious individuals who wish to know more about the emerging field of oxidative stress and aging with an emphasis on diagnostics and intervention.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Volume 1\r | 1:C | ||
| Contents | 1:xv | ||
| Acknowledgments | 1:vii | ||
| Preface | 1:ix | ||
| List of Contributors | 1:xi | ||
| SECTION 1 Historical Perspectives | 1:1 | ||
| Chapter 1 Metabolic Rate, Free Radicals and Aging | 1:3 | ||
| 1. Introduction | 1:4 | ||
| 2. Metabolic Rate and Lifespan (Rubner's Metabolic Potential) | 1:4 | ||
| 3. The Rate of Living Theory | 1:5 | ||
| 4. The Free Radical Theory of Aging | 1:7 | ||
| 5. Free Radicals, Damage and Aging | 1:8 | ||
| 6. The Oxidant/Antioxidant Equilibrium | 1:9 | ||
| 7. Active Oxygen and Signal Transduction | 1:10 | ||
| 8. Summary | 1:11 | ||
| References | 1:11 | ||
| SECTION 2 Free Radical Chemistry and Biology | 1:25 | ||
| Chapter 2 Spin-Trapping Methods for Detecting Superoxide and Hydroxyl Free Radicals In Vitro and In Vivo | 1:27 | ||
| 1. Summary | 1:28 | ||
| 2. Choice of Spin Trap | 1:28 | ||
| 3. Superoxide | 1:28 | ||
| 4. Hydroxyl Radical | 1:29 | ||
| 5. In Vivo Hydroxyl Radical Detection | 1:31 | ||
| 6. In Vivo and In Vitro Superoxide | 1:33 | ||
| 7. DTP A, EDTA, and Desferal | 1:33 | ||
| References | 1:35 | ||
| Chapter 3 Peroxyl and Alkoxyl Radical Mediated DNA Damage | 1:39 | ||
| 1. Introduction: Alkyl Radicals to Oxyradicals — The Oxygen Effect | 1:40 | ||
| 2. Lifetimes and Diffusion of Oxyradicals | 1:42 | ||
| 3. Relative Reactivities of Peroxyl and Alkoxyl Radicals | 1:44 | ||
| 4. Methods for the Generation of Peroxyl and Alkoxyl Radicals | 1:46 | ||
| 5. Peroxyl and Alkoxyl Radical Mediated DNA Strand Breaks | 1:47 | ||
| 6. DNA Base Modifications by Peroxyl and Alkoxyl Radicals | 1:48 | ||
| 7. Conclusions | 1:50 | ||
| Acknowledgment | 1:51 | ||
| References | 1:51 | ||
| Chapter 4 Nitric Oxide, Peroxynitrite and Ageing | 1:54 | ||
| 1. Introduction | 1:55 | ||
| 2. Why Do Tissues Produce Oxidants? | 1:56 | ||
| 3. Nitric Oxide | 1:57 | ||
| 4. Why is Nitric Oxide Used as an Intercellular Messenger? | 1:58 | ||
| 5. The Limited Reactivity of Nitric Oxide In Vivo | 1:59 | ||
| 6. Nitrogen Dioxide | 1:59 | ||
| 7. Peroxynitrite | 1:60 | ||
| 8. Nitrative versus Nitrosative Stress | 1:61 | ||
| 9. Tyrosine Nitration | 1:62 | ||
| 10. Alternative Mechanisms of Nitration | 1:64 | ||
| 11. Proteins Susceptible to Nitration | 1:66 | ||
| 12. Nitration of Prostacyclin Synthase | 1:66 | ||
| 13. Nitration of Structural Proteins | 1:68 | ||
| 14. Resistance to Viral Infections | 1:69 | ||
| 15. Ageing, Nitrative Stress and the Central Nervous System | 1:70 | ||
| 16. Conclusions | 1:73 | ||
| Abbreviations Used | 1:74 | ||
| References | 1:74 | ||
| SECTION 3 Redox Regulation and Cell Signaling | 1:85 | ||
| Chapter 5 Thioredoxin-Dependent Redox Regulation — Implication in Aging and Neurological Diseases | 1:87 | ||
| 1. Summary | 1:88 | ||
| 2. Introduction | 1:88 | ||
| 3. TRX and Its related Molecules | 1:89 | ||
| 4. TRX Binding Proteins | 1:90 | ||
| 5. Redox Regulation of Transcription Factors by TRX | 1:92 | ||
| 6. Redox Regulation of Apoptosis by TRX | 1:93 | ||
| 7. Cytoprotective Effects of TRX | 1:93 | ||
| 8. Aging and TRX Overexpressing Transgenic Mice | 1:94 | ||
| 9. Oxidative Stress and Central Nervous System | 1:95 | ||
| 10. Conclusion | 1:95 | ||
| References | 1:96 | ||
| Chapter 6 Redox Regulation of Genes and Cell Function | 1:102 | ||
| 1. Introduction | 1:103 | ||
| 2. The Thioredoxin System | 1:103 | ||
| 3. The Glutaredoxin System | 1:106 | ||
| 4. Redox Regulation by Thioredoxin and Glutaredoxin | 1:107 | ||
| 5. Effects of Oxidants and Antioxidants | 1:108 | ||
| 6. Future Perspectives | 1:108 | ||
| Acknowledgments | 1:109 | ||
| References | 1:109 | ||
| Chapter 7 Oxidative Stress and Signal Transduction Pathway of Redox Sensor Proteins: Clinical Applications and Novel Therapeutics | 1:112 | ||
| 1. Introduction | 1:113 | ||
| 2. Source of ROS as Signaling Molecules | 1:114 | ||
| 3. Mechanism of Oxidant Signaling | 1:114 | ||
| 4. Transcription Factor AP-1 and Its Redox Regulation | 1:115 | ||
| 5. Transcription Factor NF-қB and Its Redox Regulation | 1:116 | ||
| 6. Redox-Mediated Intervention in NF-қB Associated Diseases | 1:120 | ||
| 7. Conclusion | 1:121 | ||
| Acknowledgment | 1:121 | ||
| References | 1:122 | ||
| SECTION 4 Measurement of Oxidative Stress: Technology, Biomarkers and Applications | 1:129 | ||
| Measurement of Oxidative Stress: Technology, Biomarkers and Applications (Nucleic Acid Damage) | 1:129 | ||
| Chapter 8 Measuring Oxidative Stress and Interpreting Its Clinical Relevance for Humans | 1:131 | ||
| 1. Aging is Our | 1:132 | ||
| 2. Degenerative Effects of Aging are Universal | 1:132 | ||
| 3. Why do Humans Live So Long? It is in Our Genes | 1:133 | ||
| 4. What is Oxidative Stress? | 1:134 | ||
| 5. Measuring Oxidative Damage | 1:134 | ||
| 5.1. Alkenals | 1:136 | ||
| 5.2. Hydroperoxides (Aqueous) | 1:136 | ||
| 5.3. Hydroperoxides (Lipid) | 1:137 | ||
| 5.4. 8-Hydroxydeoxyguanosine (8-OHdG) | 1:137 | ||
| 5.5. 8-Epi-Prostaglandin F2a (8-epi-PGF2a)(Isoprostane) | 1:138 | ||
| 5.6. Urine Creatinine | 1:138 | ||
| 6. Measuring Prooxidants | 1:139 | ||
| 6.1. Antimony | 1:139 | ||
| 6.2. Arsenic | 1:139 | ||
| 6.3. C-Reactive Protein | 1:140 | ||
| 6.4. Cadmium | 1:140 | ||
| 6.5. Chromium | 1:140 | ||
| 6.6. Chlorine | 1:141 | ||
| 6.7. Iron | 1:141 | ||
| 6.8. Ferritin | 1:142 | ||
| 6.9. Copper | 1:142 | ||
| 6.10. Homocysteine | 1:142 | ||
| 6.11. Lead | 1:143 | ||
| 6.12. Manganese | 1:143 | ||
| 6.13. Mercury | 1:144 | ||
| 6.14. Nickel | 1:144 | ||
| 7. Measuring Total Antioxidant Capacity | 1:144 | ||
| 7.1. Lipid Peroxidation Inhibition Capacity (LPIC)* Assay | 1:145 | ||
| 7.2. Oxygen Radical Absorption Capacity (ORAC) Assay | 1:145 | ||
| 7.3. ORAC (Aqueous Soluble) | 1:146 | ||
| 7.4. ORAC (Lipid Soluble) | 1:147 | ||
| 8. Measuring Primary Antioxidants | 1:147 | ||
| 8.1. Available Iron Binding Capacity (AIBC) | 1:147 | ||
| 8.2. % Iron Saturation (Total Iron/TIBC)*100% | 1:148 | ||
| 8.3. Ceruloplasmin | 1:148 | ||
| 9. Measuring Secondary Antioxidants | 1:148 | ||
| 10. Aqueous Soluble Antioxidants | 1:149 | ||
| 10.1. Ascorbic Acid (vitamin C) | 1:149 | ||
| 10.2. Bilirubin (Conjugated and Total) | 1:149 | ||
| 10.3. Thiols | 1:150 | ||
| 10.4. Uric Acid | 1:150 | ||
| 11. Lipid Soluble Antioxidants | 1:150 | ||
| 11.1. α-Carotene | 1:151 | ||
| 11.2. β-Carotene | 1:151 | ||
| 11.3. β-Cryptoxanthin | 1:152 | ||
| 11.4. Lutein | 1:152 | ||
| 11.5. Lycopene | 1:153 | ||
| 11.6. Retinol (vitamin A) | 1:153 | ||
| 11.7. Retinyl Palmitate | 1:153 | ||
| 11.8. α-Tocopherol (vitamin E) | 1:154 | ||
| 11.9. δ-Tocopherol (vitamin E) | 1:154 | ||
| 11.10. γ-Tocopherol (vitamin E) | 1:155 | ||
| 11.11. Tocopherols/(Chol. + Trig.) | 1:155 | ||
| 11.12. Ubiquinol (Coenzyme Q10) | 1:155 | ||
| 11.13. Zeaxanthin | 1:156 | ||
| 12. Antioxidant Supporting Factors | 1:156 | ||
| 12.1. Albumin | 1:156 | ||
| 12.2. Total Protein | 1:157 | ||
| 12.3. Albumin/Globulins Ratio | 1:157 | ||
| 12.4. Magnesium | 1:157 | ||
| 12.5. Selenium | 1:158 | ||
| 12.6. Sulfur | 1:158 | ||
| 12.7. Zinc | 1:158 | ||
| 13. Clinical Interpretation and Use of Oxidative Stress Biomarkers for Metabolic Optimization | 1:159 | ||
| References | 1:160 | ||
| Chapter 9 Oxidative Damage to DNA: Mechanisms of Product Formation and Measurement by Mass Spectrometric Techniques | 1:165 | ||
| 1. Introduction | 1:166 | ||
| 2. Mechanisms of Oxidative Damage to DNA | 1:166 | ||
| 3. Measurement of Oxidative Damage to DNA | 1:171 | ||
| 3.1. Gas Chromatography/Mass Spectrometry | 1:172 | ||
| 4. Conclusions | 1:184 | ||
| Acknowledgment | 1:185 | ||
| References | 1:185 | ||
| Chapter 10 HPLC-MS/MS Measurement of Oxidative Base Damage to Isolated and Cellular DNA | 1:190 | ||
| 1. Introduction | 1:191 | ||
| 2. Principle of the HPLC-MS/MS Method | 1:191 | ||
| 2.1. HPLC/MS Interface | 1:191 | ||
| 2.2. Detection of the Ions | 1:192 | ||
| 3. Measurement of Oxidized Bases within DNA | 1:192 | ||
| 3.1. Set-Up of the Assay for Oxidized Bases | 1:192 | ||
| 3.2. Gamma and UV Laser Irradiation of Isolated DNA | 1:194 | ||
| 3.3. Degradation of Cellular DNA by Gamma Radiation | 1:196 | ||
| 4. Detection of Tandem Lesions within DNA | 1:197 | ||
| 4.1. Detection of Formamido/8-oxoGua within DNA | 1:197 | ||
| 4.2. Mechanistic Studies | 1:198 | ||
| 5. Conclusion | 1:199 | ||
| References | 1:200 | ||
| Chapter 11 The Use of HPLC/EC for Measurements of Oxidative DNA Damage | 1:203 | ||
| 1. Introduction | 1:204 | ||
| 2. Measurement Technologies | 1:204 | ||
| 3. GCMS | 1:206 | ||
| 4. Postlabeling | 1:206 | ||
| 5. HPLC/EC | 1:206 | ||
| 6. Column Switching HPLC/EC Method | 1:209 | ||
| 7. Conclusions | 1:213 | ||
| References | 1:214 | ||
| Chapter 12 Analysis of 8-Hydroxyguanine in DNA and Its Repair | 1:222 | ||
| 1. Introduction | 1:223 | ||
| 2. Preparation of Samples | 1:224 | ||
| 3. Measurement of 8-OH-Gua | 1:224 | ||
| 4. Endonuclease Nicking Assay | 1:225 | ||
| 5. Measurement of OGGl mRNA Level | 1:226 | ||
| 6. 8-Hydroxyguanine in Human Leukocyte DNA and Physical Exercise | 1:226 | ||
| 7. 8-Hydroxyguanine, Its Repair Activity, and Rat OGGl mRNA Induction in the Lungs of Rats Treated with Diesel Exhaust Particles | 1:229 | ||
| 8. Discussion | 1:230 | ||
| References | 1:230 | ||
| Chapter 13 HPLC-ECD, HPLC-MS/MS (Urinary Biomarkers) | 1:233 | ||
| 1. Introduction | 1:234 | ||
| 2. Principles for HPLC and GC Separation | 1:234 | ||
| 2.1. Electrochemical Detection (ECD) | 1:235 | ||
| 2.2. Mass Spectrometric Detection (MS) | 1:237 | ||
| 2.3. Immunological Methods | 1:240 | ||
| 3. Comparison of Different Methods | 1:244 | ||
| 4. Interpretation of Tissue Levels and Urinary Excretion | 1:244 | ||
| 5. What is Known from Human Studies of Biomarkers of Oxidative DNA Damage? | 1:247 | ||
| 6. Proper Design of Human Intervention Studies | 1:248 | ||
| 7. Future Perspectives | 1:250 | ||
| 8. Conclusions | 1:251 | ||
| References | 1:251 | ||
| Chapter 14 Mapping Oxidative DNA Damage at Nucleotide Resolution in Mammalian Cells | 1:257 | ||
| 1. Introduction | 1:258 | ||
| 2. Methods for Genomic DNA Sequencing | 1:259 | ||
| 3. LMPCR for the Detection of DNA Adducts in Mammalian Cells at Nucleotide Resolution | 1:262 | ||
| 4. Evolution of LMPCR Technology | 1:263 | ||
| 5. Terminal Transferase-Dependent PCR (TDPCR) | 1:266 | ||
| 6. Oxidative Base Damage at Nucleotide Resolution in Normal Human Cells | 1:268 | ||
| 7. Future Developments in Detection of Damage at Nucleotide Resolution | 1:269 | ||
| 8. Conclusion | 1:270 | ||
| Acknowledgments | 1:270 | ||
| References | 1:270 | ||
| Chapter 15 Immunochemical Detection of Oxidative DNA Damage | 1:275 | ||
| 1. Introduction | 1:276 | ||
| 2. Antibodies to Oxidation Products of DNA | 1:277 | ||
| 2.1. 5-hydroxymethyldeoxyuridine (5-HMdU) | 1:277 | ||
| 2.2. 5,6-dihydroxy-5,6-dihydrothymine (Thymine glycol) | 1:278 | ||
| 2.3. 8-oxo-2'-deoxyadenosine (8-oxodA) | 1:279 | ||
| 2.4. 8,5'-cycloadenosine-5'-monophosphate (8,5'-cyclo-AMP) | 1:279 | ||
| 2.5. 8-oxo-2'deoxyguanosine (8-oxodG) | 1:280 | ||
| 3. Pitfalls and Problems of Antibody Production | 1:287 | ||
| 4. Benefits of the Immuno-Approach | 1:287 | ||
| 5. Conclusions | 1:288 | ||
| Acknowledgments | 1:289 | ||
| References | 1:289 | ||
| Chapter 16 Postlabeling Detection of Oxidative DNA Damage | 1:294 | ||
| 1. Introduction | 1:295 | ||
| 2. Detection of 8-oxo-2'-deoxyguanosine | 1:295 | ||
| 3. Detection of Oxidative Pyrimidine Lesions | 1:299 | ||
| 4. Detection of Oxidative \"Bulky\" Lesions | 1:301 | ||
| 5. The Snake Venom Phosphodiesterase Method | 1:303 | ||
| 6. Conclusions | 1:304 | ||
| Acknowledgments | 1:304 | ||
| References | 1:305 | ||
| Chapter 17 The Comet Assay: Protective Effects of Dietary Antioxidants Against Oxidative DNA Damage Measured Using Alkaline Single Cell Gel Electrophoresis | 1:309 | ||
| 1. Introduction | 1:310 | ||
| 1.1. Background | 1:310 | ||
| 1.2. The Principle of the Comet Assay | 1:310 | ||
| 2. Method | 1:311 | ||
| 2.1. Cell Isolation | 1:313 | ||
| 2.2. Lysis | 1:313 | ||
| 2.3. Enzyme Treatment | 1:314 | ||
| 2.4. Alkaline Unwinding and Electrophoresis | 1:314 | ||
| 2.5. Neutralizing and Staining | 1:314 | ||
| 3. Oxidative DNA Damage and the Impact of Nutrition | 1:315 | ||
| 3.1. Molecular Epidemiology | 1:315 | ||
| 3.2. In Vitro Cell Studies | 1:316 | ||
| 4. Future Applications and Conclusions | 1:318 | ||
| 5. Conclusion | 1:319 | ||
| Acknowledgments | 1:320 | ||
| References | 1:320 | ||
| Measurement of Oxidative Stress: Technology, Biomarkers and Applications (Protein Damage) | 1:325 | ||
| Chapter 18 Protein Oxidation Assays | 1:327 | ||
| 1. Introduction | 1:328 | ||
| 2. Protein Carbonyl Assays Using the Spectrophotometric Method | 1:328 | ||
| 3. Protein Carbonyl Assays Using the Immunological Method | 1:330 | ||
| 4. Other Assays for Assessing Protein Oxidation | 1:332 | ||
| 5. Summary | 1:333 | ||
| References | 1:333 | ||
| Chapter 19 Effect of Oxidative Stress on Protein Synthesis | 1:336 | ||
| 1. Summary | 1:337 | ||
| 2. Introduction | 1:337 | ||
| 3. Oxidative Stress Parameter Levels in Young Rats Treated with CH and During Aging | 1:338 | ||
| 4. The Step of Protein Synthesis Most Affected by CH Treatment and Aging | 1:338 | ||
| 4.1. Effect of CH-treatment and Aging on Polypeptide Chain Completion Time (Tc) | 1:339 | ||
| 4.2. Effect of CH-treatment and Aging on Hepatic Polyribosomal Profiles | 1:340 | ||
| 5. Mechanism Underlying the Alterations in the Elongation Step in CH-treated and Old Rats: Modifications in EF-2 | 1:341 | ||
| 5.1. Comparative Effect of CH Treatment and Aging on the Amount of Absolute and Active EF-2 and on Its Oxidation State in the Rat Liver | 1:342 | ||
| 5.2. Effect of CH-treatment and Aging on State of Fragmentation of EF-2 | 1:343 | ||
| 6. Conclusions | 1:344 | ||
| Acknowledgements | 1:345 | ||
| References | 1:345 | ||
| Chapter 20 Biological Implications of Protein Oxidation | 1:350 | ||
| 1. Introduction | 1:351 | ||
| 2. Chemistry of Protein Oxidation | 1:351 | ||
| 3. Protein Oxidation as a Physiological Process | 1:352 | ||
| 4. Protein Oxidation in Diseases | 1:353 | ||
| 5. Accumulation of Oxidatively Modified Proteins in Aging | 1:354 | ||
| 6. Physical Exercise and Oxidative Stress | 1:355 | ||
| 7. Degradation of Oxidized Proteins | 1:356 | ||
| 8. Conclusion | 1:357 | ||
| References | 1:357 | ||
| Chapter 21 Application of ProteinChip® Array Technology for Detection of Protein Biomarkers of Oxidative Stress | 1:366 | ||
| 1. Introduction | 1:367 | ||
| 2. Technology Platform (SELDI TOF-MS) | 1:368 | ||
| 3. Preliminary Studies | 1:371 | ||
| 4. Conclusions/Future Directions | 1:375 | ||
| Acknowledgments | 1:377 | ||
| References | 1:377 | ||
| Measurement of Oxidative Stress: Technology, Biomarkers and Applications (Lipid Damage) | 1:381 | ||
| Chapter 22 Quantification of Isoprostanes as an Index of Oxidant Stress Status In Vivo | 1:383 | ||
| 1. Introduction | 1:384 | ||
| 2. Mechanism of Formation of the Isoprostanes | 1:384 | ||
| 3. Quantification of F2-Isoprostanes | 1:386 | ||
| 4. Isoprostane Formation In Vivo | 1:386 | ||
| 5. Measurement of the Major Urinary Metabolite of 15-F2t-Isop as an Index of Systemic Oxidant Status | 1:387 | ||
| 6. Formation of Isoprostanes in Animal Models of Oxidant Stress | 1:388 | ||
| 7. Quantification of F2-Isops in Association with Human Disease-Studies in Patients with Alzheimer's Disease | 1:389 | ||
| 8. Conclusions | 1:390 | ||
| Acknowledgments | 1:390 | ||
| References | 1:391 | ||
| Chapter 23 Analysis of Phospholipid Oxidation by Electrospray Mass Spectrometry | 1:393 | ||
| 1. Introduction | 1:394 | ||
| 2. Principles of Electrospray Mass Spectrometry (ESMS) | 1:394 | ||
| 3. Analysis of Phospholipids in Biological Samples | 1:395 | ||
| 4. Detection of Phospholipid Peroxidation in Model Lipid Systems | 1:398 | ||
| 5. Halogenated Lipid Oxidation Products Detected by ESMS | 1:401 | ||
| 6. Lipid Peroxidation Products Observed in Biological and Clinical Samples | 1:402 | ||
| 7. Quantitation in ESMS | 1:405 | ||
| 8. Conclusions | 1:406 | ||
| Abbreviations | 1:406 | ||
| Acknowledgments | 1:406 | ||
| References | 1:406 | ||
| Measurement of Oxidative Stress: Technology, Biomarkers and Applications (Carbohydrate Damage) | 1:411 | ||
| Chapter 24 Glycoxidative and Carbonyl Stress in Aging and Age-Related Diseases | 1:413 | ||
| 1. Introduction | 1:414 | ||
| 2. Chemical Pathways of the Maillard Reaction In Vivo | 1:415 | ||
| 3. Metal- and Non-Metal Catalyzed Oxidation During Protein Glycation | 1:417 | ||
| 3.1. Glucose Autoxidation and Glycoxidation | 1:417 | ||
| 3.2. Metal-Binding and Free Radical Generation by Glycated Proteins | 1:418 | ||
| 3.3. Carboxymethyl-Lysine: A Molecular \"Sink\" of the Aging Process | 1:419 | ||
| 3.4. Non-Metal Catalyzed Generation of Free Radicals | 1:422 | ||
| 4. Induction of Cellular Oxidative Stress by Advanced Glycation Endproducts | 1:422 | ||
| 4.1. RAGE Activation, Oxidative Stress and NF-қB Activation | 1:422 | ||
| 4.2. Methylglyoxal Modification of Albumin and Cellular Oxidative Stress | 1:424 | ||
| 5. Advanced Glycation Products as Markers of Longevity | 1:424 | ||
| 6. Conclusions | 1:425 | ||
| Acknowledgments | 1:426 | ||
| References | 1:426 | ||
| Measurement of Oxidative Stress: Technology, Biomarkers and Applications (Mitochondrial Damage) | 1:435 | ||
| Chapter 25 Mitochondrial Mutations in Vertebrate Aging | 1:437 | ||
| 1. Scope of This Review | 1:438 | ||
| 2. Origins of the Mitochondrial DNA Theory of Aging | 1:438 | ||
| 3. Elaborations Founded on Implausible Population Dynamics | 1:439 | ||
| 4. Clonal Expansion of Mutant mtDNA | 1:440 | ||
| 5. Clonal Expansion Challenges the \"Tip of the Iceberg\" Theory | 1:441 | ||
| 6. Once You Have Eliminated the Impossible ... | 1:444 | ||
| References | 1:447 | ||
| Chapter 26 Mitochondria, Oxidative Stress and Mitochondrial Diseases | 1:452 | ||
| 1. Introduction | 1:453 | ||
| 2. Mitochondria Perform Multiple Cellular Functions | 1:455 | ||
| 3. Mitochondrial DNA is Maternally Inherited | 1:455 | ||
| 4. Mitochondrial DNA is Susceptible to Oxidative Damage | 1:456 | ||
| 5. Oxidative Damage to Mitochondrial DNA and Its Repair | 1:457 | ||
| 6. Mitochondrial Damage Checkpoint: Monitoring the Functional State of Mitochondria | 1:457 | ||
| 7. mtDNA Mutations and Aging | 1:459 | ||
| 8. mtDNA Mutations and Mitochondrial Diseases | 1:460 | ||
| 9. mtDNA Mutations and Cancer | 1:460 | ||
| 10. Perspective | 1:461 | ||
| Acknowledgment | 1:461 | ||
| References | 1:462 | ||
| Measurement of Oxidative Stress: Technology, Biomarkers and Applications (Standards for Oxidative Stress Measurements) | 1:467 | ||
| Chapter 27 Oxidative DNA Damage Biomarkers: A Need for Quality Control | 1:469 | ||
| 1. Introduction | 1:470 | ||
| 2. Measuring Oxidative DNA Damage | 1:471 | ||
| 2.1. Different Analytical Approaches | 1:471 | ||
| 2.2. The Range of Values of 8-oxoguanine in Human Cells | 1:472 | ||
| 2.3. Reasons for the Discrepancies in Measurement of 8-oxoguanine | 1:473 | ||
| 2.4. The ESCODD Approach | 1:475 | ||
| 2.5. Optimizing 8-oxoguanine Estimation; What do We Know So Far? | 1:478 | ||
| 2.6. How Do the Different Approaches Compare? | 1:479 | ||
| 3. Conclusions | 1:480 | ||
| Acknowledgments | 1:481 | ||
| References | 1:481 | ||
| SECTION 5 Dietary Antioxidants | 1:485 | ||
| Chapter 28 Dietary Antioxidants — Human Studies Overview | 1:487 | ||
| 1. Introduction | 1:488 | ||
| 2. Assessment of Antioxidant Intake and Status | 1:489 | ||
| 2.1. Vitamin E | 1:489 | ||
| 2.2. Carotenoids | 1:489 | ||
| 2.3. Vitamin C | 1:490 | ||
| 2.4. Phenolic Antioxidants | 1:490 | ||
| 3. Biomarkers of Oxidative Stress Status | 1:491 | ||
| 3.1. Biomarkers of Lipid Oxidation | 1:491 | ||
| 3.2. Biomarkers of Protein Oxidation | 1:493 | ||
| 3.3. Biomarkers of DNA Oxidation | 1:493 | ||
| 4. Standards of Evidence | 1:494 | ||
| 5. Hierarchy of Research Designs | 1:495 | ||
| 6. Conclusion | 1:497 | ||
| References | 1:497 | ||
| Chapter 29 Current Status of the Potential Role of Flavonoids in Neuroprotection | 1:503 | ||
| 1. Introduction | 1:504 | ||
| 2. Oxidative Stress and the Brain | 1:504 | ||
| 3. Flavonoids as Free Radical Scavengers | 1:506 | ||
| 4. Biological Properties Independent of Free Radical Scavenging | 1:509 | ||
| 5. Biotransformation of Flavonoids | 1:510 | ||
| 6. Interactions of Flavonoids with Cells Derived from the CNS | 1:512 | ||
| 7. Mechanisms of Lipid Peroxide-Induced Neuronal Dysfunction Involving Mitogen Activated Kinases | 1:514 | ||
| Acknowledgments | 1:515 | ||
| References | 1:515 | ||
| Chapter 30 Neurological Aging and Nutritional Intervention | 1:526 | ||
| 1. Introduction | 1:527 | ||
| 2. Phytochemicals in Fruits and Vegetables | 1:528 | ||
| 3. Fruits and Vegetables: Antioxidants and Anti-Inflammatories | 1:529 | ||
| 3.1. Spinach and Strawberries | 1:529 | ||
| 3.2. Blueberries | 1:530 | ||
| 3.3. Aged Garlic Extract | 1:532 | ||
| 3.4. Red Bell Pepper | 1:532 | ||
| 3.5. Tomatoes | 1:533 | ||
| 4. Beverages: Antioxidants and Anti-Inflammatories | 1:533 | ||
| 4.1. Wine | 1:533 | ||
| 4.2. Tea | 1:533 | ||
| 5. Conclusions | 1:534 | ||
| Acknowledgments | 1:534 | ||
| References | 1:535 | ||
| Chapter 31 Comparative Study on Antioxidant Activity Against Lipid Peroxidation | 1:543 | ||
| 1. Introduction | 1:544 | ||
| 2. Inhibition of Lipid Peroxidation by Antioxidant | 1:544 | ||
| 3. Reactivity of the Antioxidant Toward Radicals | 1:545 | ||
| 4. Fate of Antioxidant-Derived Radical | 1:549 | ||
| 5. Location of Antioxidant | 1:550 | ||
| 6. Interactions between Antioxidants | 1:551 | ||
| 7. Pro-Oxidant Action of Antioxidant | 1:551 | ||
| 8. Metabolites | 1:552 | ||
| 9. Concluding Remarks | 1:553 | ||
| References | 1:553 | ||
| Chapter 32 α -Tocopherol: Beyond the Antioxidant Dogma | 1:555 | ||
| 1. Introduction | 1:556 | ||
| 2. Uptake and Transport | 1:556 | ||
| 3. Vitamin E Deficiency | 1:557 | ||
| 4. Non-Antioxidant Molecular Mechanisms | 1:560 | ||
| 5. Protein Kinase C Regulation | 1:562 | ||
| 5.1. Inhibition by α-Tocopherol is not Caused by a Direct Interaction with Protein Kinase C | 1:562 | ||
| 5.2. α-Tocopherol Inhibits Protein Kinase C Phosphorylation-State and Activity, not Expression | 1:563 | ||
| 5.3. Effect on Gene Expression | 1:563 | ||
| 6. Effects of Tocopherols on Cell Proliferation | 1:563 | ||
| 7. Conclusions | 1:564 | ||
| Acknowledgments | 1:564 | ||
| References | 1:564 | ||
| Chapter 33 γ-Tocopherol, the Neglected Form of Vitamin E: New Functions, New Interest | 1:569 | ||
| 1. Introduction | 1:570 | ||
| 2. Bio-Availability and Bio-Activity | 1:570 | ||
| 3. Absorption and Metabolism | 1:571 | ||
| 4. Biochemistry of γT | 1:573 | ||
| 5. Non-Antioxidant Activity | 1:574 | ||
| 6. γT and Coronary Heart Disease | 1:575 | ||
| 7. Summary | 1:576 | ||
| Acknowledgments | 1:577 | ||
| References | 1:577 | ||
| Chapter 34 Ascorbic Acid DNA Damage and Repair | 1:583 | ||
| 1. Introduction | 1:584 | ||
| 2. Recommendations on Maximum Intake | 1:584 | ||
| 3. Metabolism of Ascorbic Acid | 1:585 | ||
| 4. Properties | 1:585 | ||
| 5. Adverse Effects | 1:585 | ||
| 6. Ascorbic Acid — Antioxidant or Pro-Oxidant | 1:586 | ||
| 7. Ascorbic Acid Intervention | 1:587 | ||
| 8. Measuring Oxidative Damage to DNA | 1:587 | ||
| 9. Urine and Serum Levels of 8-oxo-dG | 1:589 | ||
| 10. Ascorbic Acid and DNA Repair | 1:591 | ||
| 11. Redox Regulation of AP-1 | 1:591 | ||
| 12. AP-1 Binding and DNA Repair | 1:594 | ||
| 13, Conclusions | 1:594 | ||
| Acknowledgments | 1:595 | ||
| References | 1:595 | ||
| Chapter 35 Carotenoids and Oxidative Stress | 1:598 | ||
| 1. Introduction | 1:599 | ||
| 2. Carotenoids as Antioxidants | 1:599 | ||
| 2.1. In vitro Studies | 1:599 | ||
| 2.2. Ex vivo Studies | 1:600 | ||
| 2.3. In vivo Studies | 1:601 | ||
| 3. Carotenoids as Pro-Oxidants | 1:603 | ||
| 4. Carotenoids and Aging | 1:604 | ||
| 5. Summary | 1:605 | ||
| References | 1:605 | ||
| Chapter 36 Functional Foods | 1:612 | ||
| 1. Introduction | 1:613 | ||
| 2. Definition of Functional Foods | 1:613 | ||
| 3. Definition of Food for Specific Health Use (FOSHU) | 1:615 | ||
| 4. Case of \"Functional Foods\" for Prevention of Oxidative Stress | 1:616 | ||
| 5. Dietary Antioxidants as Functional Foods | 1:617 | ||
| 6. Conclusion | 1:619 | ||
| References | 1:620 | ||
| Chapter 37 Nutrition and Phase II Reactions —The Role of Glutathione | 1:624 | ||
| 1. Introduction | 1:625 | ||
| 2. Glutathione in Phase II Reaction and Cell Signal Transduction | 1:625 | ||
| 3. Glutathione and Thioredoxin: A \"Parallel\" Redox Regulation System | 1:628 | ||
| 4. Glutathione: Synthesis, Nutritional Modulation, and Its Clinical Implication | 1:629 | ||
| 5. Glutathione-S-Transferase and Phytochemicals: Implications in Health and Disease | 1:633 | ||
| 6. Summary | 1:634 | ||
| References | 1:635 | ||
| Chapter 38 Oligomeric Proanthocyanidins in Human Health and Disease Prevention | 1:640 | ||
| 1. Introduction | 1:641 | ||
| 2. French Paradox and Oligomeric Proanthocyanidins (OPC) | 1:641 | ||
| 3. Chemistry of Polyphenols and Oligomeric Proanthocyanidins | 1:642 | ||
| 4. Occurrence of Oligomeric Proanthocyanidins in Food and Beverage | 1:645 | ||
| 5. Dietary Intake and Bioavailability of Oligomeric Proanthocyanidins | 1:646 | ||
| 6. Nutritional Benefits of Oligomeric Proanthocyanidins (OPC) | 1:647 | ||
| 7. Recent Advances in Natural Grape Seed Proanthocyanidin Research | 1:648 | ||
| 7.1. Safety of GSPE | 1:648 | ||
| 7.2. Free Radical Scavenging Activity | 1:649 | ||
| 7.3. Protection Against Drug- and Chemical-Induced Multiorgan Toxicity | 1:649 | ||
| 7.4. Cardioprotection | 1:650 | ||
| 7.5. Protection Against Stress-Induced Oxidative Gastrointestinal Injury | 1:651 | ||
| 7.6. Cancer Chemoprevention | 1:651 | ||
| 7.7. Age-Related Hypertension and Glycosylated Hemoglobin Study | 1:652 | ||
| 7.8. Improvement of Lipid Profile in Hypercholesterolemic Human Subjects | 1:652 | ||
| 7.9. Inflammation, Angiogenesis, SPF and Skin Health | 1:653 | ||
| 7.10. Human Pancreatitis Study | 1:654 | ||
| 7.11. Mechanistic Pathways of Cytoprotection by GSPE | 1:654 | ||
| 8. Conclusion | 1:655 | ||
| References | 1:655 | ||
| Chapter 39 Effects of Antioxidant Vitamins C and E on Gene Expression in the Vasculature | 1:661 | ||
| 1. Introduction | 1:662 | ||
| 2. Redox Sensitive Transcription Factors | 1:662 | ||
| 3. Nuclear Factor Kappa Binding Protein NF-қB | 1:662 | ||
| 4. Activator Protein 1 (API) | 1:664 | ||
| 5. Vitamin C Effects on Gene Expression in the Vasculature | 1:664 | ||
| 6. Vitamin E Effects on Gene Expression in the Vasculature | 1:668 | ||
| 7. Conclusions | 1:670 | ||
| Acknowledgments | 1:670 | ||
| References | 1:671 | ||
| SECTION 6 Endogenous Antioxidants and Repair | 1:677 | ||
| Chapter 40 Oxidative Defense Mechanisms | 1:679 | ||
| 1. Introduction | 1:680 | ||
| 2. Antioxidant Enzymes and Compounds | 1:681 | ||
| 3. DNA Repair | 1:681 | ||
| 4. Lipid Degradation and Repair | 1:682 | ||
| 5. Protein Degradation | 1:682 | ||
| 6. Adaptive Response | 1:683 | ||
| 7. Conclusions | 1:684 | ||
| Acknowledgments | 1:684 | ||
| References | 1:684 | ||
| Chapter 41 Heme Oxygenase: Its Regulation and Role | 1:690 | ||
| 1. Introduction | 1:691 | ||
| 2. General Characteristics and Isoforms of Heme Oxygenase | 1:691 | ||
| 3. Functions of the Products of the HO Reaction | 1:694 | ||
| 3.1. Carbon Monoxide (CO) | 1:694 | ||
| 3.2. Biliverdin and Bilirubin | 1:695 | ||
| 3.3. Iron | 1:695 | ||
| 4. Regulation of Expression of HO-1 | 1:695 | ||
| 4.1. Structure of the HO-1 Gene and Its Promoter and Enhancer Regions | 1:697 | ||
| 5. Anti-Inflammatory and Antioxidant Properties of HO-1 | 1:699 | ||
| 6. Heme Oxygenase and Aging | 1:700 | ||
| Acknowledgments | 1:700 | ||
| References | 1:701 | ||
| Chapter 42 Metallothioneins | 1:707 | ||
| 1. Introduction | 1:708 | ||
| 2. Antioxidant Action of MTs | 1:708 | ||
| 2.1. Evidence Obtained from In Vitro Studies | 1:708 | ||
| 2.2. Evidence Obtained from Studies Using Cultured Cells | 1:709 | ||
| 2.3. Evidence Obtained from Intact Animal Studies | 1:709 | ||
| 2.4. Direct Evidence Obtained from Genetically Altered Mouse Models | 1:710 | ||
| 3. Possible Mechanisms of Antioxidant Action of MTs | 1:712 | ||
| 4. MTs and Aging | 1:713 | ||
| 5. Conclusion | 1:714 | ||
| Acknowledgments | 1:714 | ||
| References | 1:714 | ||
| Chapter 43 Human Genomic DNA Repair Enzymes | 1:719 | ||
| 1. Introduction | 1:720 | ||
| 2. DNA Repair Systems | 1:722 | ||
| 3. DNA Polymerases, a Central Role in DNA Repair | 1:722 | ||
| 4. Nucleotide Excision Repair (NER) | 1:723 | ||
| 5. Base Excision Repair (BER) | 1:726 | ||
| 6. Reversal of DNA Damage | 1:726 | ||
| 7. Single-Strand Break Repair | 1:726 | ||
| 8. Double-Strand Break Repair (DSBR) | 1:728 | ||
| 9. Mismatch Repair (MMR) | 1:728 | ||
| 10. Repair of DNA-DNA and Protein-DNA Crosslinks | 1:730 | ||
| 11. DNA Repair Heterogeneity | 1:730 | ||
| 12. Regulation of DNA Repair Genes | 1:732 | ||
| 13. Human DNA Repair Syndromes | 1:733 | ||
| 14. Conclusion | 1:734 | ||
| Acknowledgments | 1:734 | ||
| References | 1:734 | ||
| Chapter 44 DNA Repair in Mammalian Mitochondria | 1:744 | ||
| 1. Introduction | 1:745 | ||
| 2. DNA Repair Mechanisms in Mammalian Mitochondria | 1:745 | ||
| 3. Base Excision Repair Pathways in Mitochondria | 1:747 | ||
| 4. DNA Glycosylases in Mammalian Mitochondria | 1:749 | ||
| 4.1. UDG1 | 1:749 | ||
| 4.2. mtODE (Mitochondrial Oxidative Damage Endonuclease) | 1:750 | ||
| 4.3. mtTGEndo (Mitochondrial Thymine Glycol Endonuclease) | 1:751 | ||
| 5. Other Mitochondrial Enzymes Involved in DNA Repair | 1:751 | ||
| 5.1. DNA Polymerase Gamma | 1:751 | ||
| 5.2. AP Endonucleases | 1:751 | ||
| 5.3. Damage Reversal | 1:752 | ||
| 5.4. Mismatch Repair | 1:752 | ||
| 5.5. Recombinational Repair | 1:753 | ||
| 6. Changes in mtDNA Repair with Age | 1:753 | ||
| 7. Perspectives | 1:754 | ||
| Acknowledgment | 1:755 | ||
| References | 1:755 | ||
| Chapter 45 α-Lipoic Acid | 1:759 | ||
| 1. Introduction | 1:760 | ||
| 2. Reduction of Lipoate to Dihydrolipoate: The Metabolic Antioxidant | 1:760 | ||
| 3. Lipoyl Residues in Oxidative Metabolism | 1:762 | ||
| 4. Redox Properties: Biological Implications | 1:763 | ||
| 4.1. NF-қB | 1:763 | ||
| 4.2. Acquired Immunodeficiency Syndrome (AIDS) | 1:766 | ||
| 4.3. Caspase-Dependent Cell Death | 1:768 | ||
| 4.4. Cell Adhesion | 1:770 | ||
| 4.5. Reductive Stress | 1:771 | ||
| 4.6. Glucose Uptake | 1:771 | ||
| 4.7. A Novel Form of Lipoic Acid | 1:772 | ||
| 5. Conclusion | 1:774 | ||
| Acknowledgment | 1:774 | ||
| References | 1:774 | ||
| Chapter 46 Coenzyme Q10 Prevents DNA Oxidation and Enhances Recovery from Oxidative Damage | 1:784 | ||
| 1. Introduction | 1:785 | ||
| 2. DNA Damage and Repair Systems | 1:786 | ||
| 3. Oxidative DNA Damage and Recovery in DNA of Lymphocytes In Vitro Enriched with Ubiquinol-10 or Ubiquinone-10 | 1:788 | ||
| 4. Effect of CoQ10 In Vivo Supplementation on DNA Damage and Its Repair in Primary Cultured Lymphocytes | 1:795 | ||
| 5. Effect of In Vivo CoQ10 Supplementation on DNA Repair Enzyme Expression | 1:798 | ||
| 6. Conclusion | 1:799 | ||
| Acknowledgments | 1:801 | ||
| References | 1:801 | ||
| Chapter 47 In Vivo Assessment of Antioxidant Status | 1:806 | ||
| 1. Summary | 1:807 | ||
| 2. Introduction | 1:807 | ||
| 3. Dietary Intake of Antioxidants | 1:809 | ||
| 4. Measurement of Individual Antioxidants | 1:810 | ||
| 5. Total Antioxidant Capacity | 1:811 | ||
| 6. Pitfalls in the Methods of Assessment | 1:814 | ||
| 7. Conclusion | 1:816 | ||
| Acknowledgments | 1:817 | ||
| References | 1:817 | ||
| Index | I-1 | ||
| Volume 2\r | 2:C | ||
| Contents | 2:xv | ||
| Acknowledgments | 2:vii | ||
| Preface | 2:ix | ||
| List of Contributors | 2:xi | ||
| VOLUME 2 | 2:823 | ||
| SECTION 7 Epidemiology and Intervention Studies | 2:823 | ||
| 48 Epidemiology of Antioxidants in Cancer and Cardiovascular Disease | 2:825 | ||
| 1. Introduction | 2:826 | ||
| 2. Understanding Cancer | 2:826 | ||
| 3. Epidemiology of Twin Studies | 2:832 | ||
| 4. Rate of Knowledge Expansion in Medicine | 2:834 | ||
| 5. Vitamin Supplements and Cancer Prevention | 2:836 | ||
| 6. Cardiovascular Disease | 2:843 | ||
| 7. Conclusion | 2:844 | ||
| References | 2:846 | ||
| 49 Oxidative Stress and Antioxidant Intervention | 2:849 | ||
| 1. Introduction | 2:850 | ||
| 2. Lipid Peroxidation and Antioxidants | 2:850 | ||
| 3. Vitamin E | 2:853 | ||
| 3.1. Vitamin E Levels in Cells can be Manipulated | 2:853 | ||
| 3.2. In Vivo Photoprotection by Vitamin E | 2:856 | ||
| 4. Nitric Oxide as an Antioxidant | 2:858 | ||
| 4.1. A Theoretical Comparison of 'NO and Vitamin E as Cell Membrane-Antioxidants | 2:858 | ||
| 5. Vitamin C | 2:860 | ||
| 5.1. Ascorbate, the Terminal Small-Molecule Antioxidant | 2:860 | ||
| 5.2. Ascorbate can be a Pro-Oxidant | 2:861 | ||
| 6. Antioxidant Network | 2:862 | ||
| 7. Aging | 2:863 | ||
| 8. Summary | 2:863 | ||
| 9. Abbreviations | 2:864 | ||
| References | 2:864 | ||
| 50 Oxidative Stress in Human Populations | 2:870 | ||
| 1. Summary | 2:871 | ||
| 2. Introduction | 2:871 | ||
| 3. Methods | 2:872 | ||
| 4. Results | 2:876 | ||
| 5. Discussion | 2:877 | ||
| 6. Conclusion | 2:879 | ||
| References | 2:879 | ||
| SECTION 8 Oxidative Stress Related Diseases | 2:881 | ||
| 51 Oxidative Stress Related Diseases — Overview | 2:883 | ||
| 1. Introduction | 2:884 | ||
| 2. Mitochondrial Injury | 2:885 | ||
| 3. Inflammation | 2:886 | ||
| 4. The Balance between Superoxide and Superoxide Dismutases | 2:887 | ||
| 5. Other Ways of Upsetting the Balance | 2:888 | ||
| 6. SOD Deficiency | 2:890 | ||
| 7. Oxidative Stress and Malignancy | 2:891 | ||
| References | 2:892 | ||
| 52 Role of Oxidative Stress and Other Novel Risk Factors in Cardiovascular Disease | 2:896 | ||
| 1. Introduction | 2:897 | ||
| 2. Mechanisms of Atherosclerosis and Cardiovascular Events | 2:898 | ||
| 2.1. Role of Modified Lipoproteins | 2:898 | ||
| 2.2. Artery Wall Inflammation | 2:899 | ||
| 2.3. Endothelial Cell Activation/Injury | 2:900 | ||
| 2.4. Systemic Inflammation and Plasma Markers | 2:901 | ||
| 3. Evidence of Enhanced Oxidative Stress and Increased Novel CVRF in Individuals at High Risk for Cardiovascular Disease | 2:901 | ||
| 3.1. Diabetic Dyslipidemia | 2:902 | ||
| 3.2. Oxidative Stress and Lipoprotein Oxidation | 2:904 | ||
| 3.3. Advanced Glycation Endproducts | 2:906 | ||
| 3.4. Endothelial Cell Activation/Injury and Dysfunction | 2:907 | ||
| 3.5. Systemic Inflammation | 2:909 | ||
| 4. Conclusion | 2:910 | ||
| References | 2:910 | ||
| 53 Overview of Oxidative Stress and Cancer | 2:925 | ||
| 1. Introduction | 2:926 | ||
| 2. Oxidative Stress and Cell Pathophysiology | 2:926 | ||
| 2.1. Oxidative DNA Damage Induced by Endogenous and Environmental Carcinogens | 2:926 | ||
| 2.2. Mutagenesis | 2:926 | ||
| 2.3. Growth Promotion | 2:928 | ||
| 3. Animal Models-Induction of Tumors by Oxidants | 2:929 | ||
| 4. Evidence for Role of Oxidative Stress in Human Carcinogenesis | 2:930 | ||
| 4.1. Intermediate Markers of Oxidative Stress | 2:930 | ||
| 4.2. Human Epidemiologic Studies Attempting to Link Oxidative Stress and Cancer | 2:933 | ||
| 5. Conclusions | 2:935 | ||
| References | 2:936 | ||
| 54 Oxidative Stress and Skin Cancer | 2:955 | ||
| 1. Introduction | 2:956 | ||
| 2. Light, Oxidation and DNA Damage | 2:956 | ||
| 3. Basal Cell Carcinoma (BCC) | 2:957 | ||
| 4. Genetics | 2:957 | ||
| 5. Oxidative Stress and Apoptosis | 2:957 | ||
| 6. Actinic Keratoses (AK) and Squamous Cell Carcinoma (SCC) | 2:958 | ||
| 7. Treatment | 2:958 | ||
| 8. p53 | 2:959 | ||
| 9. Melanoma | 2:959 | ||
| 10. Treatment | 2:960 | ||
| 11. Melanoma and Oxidative Metabolism | 2:960 | ||
| 12. Conclusion | 2:961 | ||
| References | 2:961 | ||
| 55 Modification of Endogenous Antioxidant Enzymes in the Brain as Well as Extra-Brain Tissues by Propargylamines: Is it Related to the Life Prolonging Effect of (-)Deprenyl | 2:966 | ||
| 1. Summary | 2:967 | ||
| 2. Introduction | 2:967 | ||
| 3. Changes in Endogenous Antioxidant Enzyme Activities with Age | 2:969 | ||
| 4. Antioxidant Enzyme Upregulation: Common Properties of Propargylamines | 2:972 | ||
| 5. Variability of an Optimal Dose of (-)Deprenyl on Antioxidant Enzyme Upregulation | 2:975 | ||
| 6. Possible Roles of Upregulation of Antioxidant Enzymes in Life Span Extension of Animals | 2:978 | ||
| 7. Neurohumoral Events Affected by (-)Deprenyl | 2:979 | ||
| 8. Conclusions | 2:979 | ||
| Acknowledgments | 2:980 | ||
| References | 2:980 | ||
| 56 Oxidative Stress and Age-Related Macular Degeneration | 2:987 | ||
| 1. Introduction | 2:988 | ||
| 2. Multiple Factors Contribute to AMD | 2:989 | ||
| 3. Oxidative Stress and AMD | 2:990 | ||
| 4. Age-Related Changes of Plasma Antioxidants | 2:991 | ||
| 4.1. Glutathione | 2:991 | ||
| 4.2. Carotenoids | 2:992 | ||
| 5. Mitochondria of RPE as a Target of Oxidative Injury | 2:992 | ||
| 6. Protection of RPE by Detoxification Enzyme Inducers | 2:993 | ||
| 7. Conclusion | 2:994 | ||
| Acknowledgments | 2:994 | ||
| References | 2:995 | ||
| 57 Preeclampsia and Antioxidants | 2:999 | ||
| 1. Introduction | 2:1000 | ||
| 2. Antioxidant Levels in Peripheral Blood | 2:1000 | ||
| 2.1. Lipid Peroxidation | 2:1000 | ||
| 2.2. Neutrophils | 2:1001 | ||
| 2.3. Glutathione | 2:1001 | ||
| 3. Placental Antioxidant Levels | 2:1003 | ||
| 3.1. Lipid Peroxides | 2:1003 | ||
| 3.2. The Role of Superoxide in Lipid Peroxide Generation | 2:1003 | ||
| 4. Antioxidants and the Treatment of Preeclampsia | 2:1004 | ||
| 4.1. Vitamin E | 2:1004 | ||
| 4.2. Vitamin C | 2:1004 | ||
| 5. Antioxidants and the Immune System | 2:1005 | ||
| 5.1. TNF-α | 2:1005 | ||
| 5.2. Glutathione | 2:1005 | ||
| 5.3 Nitric Oxide | 2:1006 | ||
| 5.4. IL-6 | 2:1006 | ||
| 6. Conclusion | 2:1007 | ||
| References | 2:1007 | ||
| 58 Iron Regulation, Hemochromatosis, and Cancer | 2:1011 | ||
| 1. Introduction | 2:1012 | ||
| 2. Fenton Chemistry and \"Free\" Iron | 2:1012 | ||
| 3. \"Free\" Iron in the Biological Environment | 2:1013 | ||
| 4. Significance of Superoxide in Iron-Dependent Oxidative Damage | 2:1013 | ||
| 5. Iron Transporter | 2:1014 | ||
| 6. Post-transcriptional Regulation of Iron Metabolism | 2:1015 | ||
| 7. Hemochromatosis | 2:1015 | ||
| 8. Iron and Carcinogenesis in Humans | 2:1017 | ||
| 9. Iron and Carcinogenesis in Animals | 2:1017 | ||
| 10. Target Genes of Oxidative Stress-Induced Carcinogenesis | 2:1018 | ||
| 11. Conclusion | 2:1019 | ||
| Acknowledgments | 2:1019 | ||
| References | 2:1019 | ||
| SECTION 9 Aging and Oxidative Stress | 2:1027 | ||
| 59 Aging and Oxidative Stress in Transgenic Mice | 2:1029 | ||
| 1. Summary | 2:1030 | ||
| 2. Introduction | 2:1030 | ||
| 3. Transgenic/Knockout Mouse Models with Alterations in the Antioxidant Defense System | 2:1032 | ||
| 3.1. Transgenic Mice Overexpressing Antioxidant Genes | 2:1032 | ||
| 3.2. Knockout Mice Showing Reduced Expression of Antioxidant Genes | 2:1040 | ||
| 4. Transgenic/Knockout Mouse Models Used to Study the Role of Oxidative Stress in Aging | 2:1043 | ||
| 4.1. Transgenic Mice Overexpressing CuZnSOD | 2:1043 | ||
| 4.2. Transgenic Mice Deficient in p66shc | 2:1044 | ||
| 4.3. Transgenic Mice Deficient in MnSOD | 2:1045 | ||
| Acknowledgments | 2:1046 | ||
| References | 2:1046 | ||
| 60 Caloric Restriction, Aging and Oxidative Stress | 2:1061 | ||
| 1. Introduction | 2:1062 | ||
| 2. Extension of Maximum Life-Span | 2:1062 | ||
| 3. Attenuation of Oxidative Damage and the Associated Decline in Function | 2:1063 | ||
| 4. New Directions in Caloric Restriction Research | 2:1064 | ||
| 4.1. Caloric Restriction and Environmental Stress | 2:1064 | ||
| 4.2. Gene Expression Profiles | 2:1065 | ||
| 4.3. Nonhuman Primate Studies | 2:1066 | ||
| 5. Conclusions | 2:1066 | ||
| Acknowledgments | 2:1067 | ||
| References | 2:1067 | ||
| 61 Hormones and Oxidative Stress | 2:1070 | ||
| 1. Introduction | 2:1071 | ||
| 2. Growth Hormone and IGF-I | 2:1071 | ||
| 3. Insulin, Glucose, and Diabetes | 2:1075 | ||
| 4. Estrogens | 2:1081 | ||
| 5. Thyroid Hormones | 2:1086 | ||
| 6. Adrenal Hormones | 2:1092 | ||
| 6.1. DHEA | 2:1092 | ||
| 6.2. Glucocorticoids | 2:1095 | ||
| 7. Conclusion | 2:1097 | ||
| References | 2:1097 | ||
| 62 Exercise | 2:1120 | ||
| 1. Introduction | 2:1121 | ||
| 2. Exercise Principles | 2:1121 | ||
| 3. Aging Principles | 2:1122 | ||
| 4. Pleiotropic and Hormetic Effects of Exercise and Aging | 2:1122 | ||
| 5. Exercise-Induced Oxidative Stress | 2:1124 | ||
| 6. Exercise as a Prevention Against Oxidative Stress | 2:1126 | ||
| 7. Different Exercise Protocols | 2:1127 | ||
| 8. Conclusion | 2:1128 | ||
| Acknowledgments | 2:1128 | ||
| References | 2:1128 | ||
| SECTION 10 Evolutionary Comparative Biology of Aging and Longevity | 2:1133 | ||
| 63 Evolutionary Basis of Human Aging | 2:1135 | ||
| 1. The Evolutionary Theory of Senescence | 2:1136 | ||
| 2. Comparative Studies of Aging and Longevity | 2:1137 | ||
| 3. Evolutionary Basis of Life Extension Through Calorie Restriction | 2:1138 | ||
| 4. Evolution of Human Reproductive Senescence | 2:1140 | ||
| 5. Evolution of Germ-Line Immortality | 2:1141 | ||
| 6. Human Aging and Oxidative Stress | 2:1142 | ||
| References | 2:1142 | ||
| 64 Genetic Stability, Dysdifferentiation, and Longevity Determinant Genes | 2:1146 | ||
| 1. Biology of Human Aging | 2:1147 | ||
| 1.1. The Human Survival Curve | 2:1147 | ||
| 1.2. Physiology of Human Aging | 2:1151 | ||
| 1.3. Diseases of Human Aging | 2:1155 | ||
| 1.4. Economic Impact of Aging | 2:1158 | ||
| 1.5. Complexity of Aging | 2:1161 | ||
| 2. Evolutionary and Comparative Biology Studies | 2:1162 | ||
| 2.1. The Pleiotropic Antagonistic Hypothesis of Aging | 2:1162 | ||
| 2.2. The Disposal Soma Hypothesis of Aging | 2:1165 | ||
| 3. The Genetic Complexity of Aging and Longevity Processes | 2:1168 | ||
| 4. What are the Longevity Determinant Genes | 2:1172 | ||
| 4.1. Rate of Development as a Function of Lifespan | 2:1174 | ||
| 4.2. Evolution of Human Neotenous Traits | 2:1175 | ||
| 4.3. Lifespan Energy Potential | 2:1176 | ||
| 4.4. Other Parameters that are Unique to Human | 2:1177 | ||
| 4.5. DNA Repair Levels as a Function of Lifespan | 2:1178 | ||
| 4.6. Antioxidant Levels as a Function of Lifespan | 2:1179 | ||
| 4.6.1. Superoxide Dismutase | 2:1179 | ||
| 4.6.2. Dietary Antioxidants | 2:1185 | ||
| 4.6.3. Carotinoids | 2:1186 | ||
| 4.6.4. Vitamin C | 2:1187 | ||
| 4.6.5. Antioxidants having Negative Correlation with Lifespan | 2:1188 | ||
| 4.6.6. Uric Acid | 2:1189 | ||
| 4.6.7. Total Antioxidant Capacity | 2:1190 | ||
| 4.6.8. P450 Cytochrome Detoxification System | 2:1191 | ||
| 4.6.9. Rate of Auto-oxidation of Tissue Homogenates | 2:1192 | ||
| 5. DNA Oxidative Damage | 2:1193 | ||
| 6. Glycation and Glycoxidation | 2:1194 | ||
| 7. Genetic Stability, Cancer and the Dysdifferentiation Hypothesis of Aging | 2:1195 | ||
| 8. Recent Support from Other Laboratories | 2:1201 | ||
| 8.1. Hominid Evolution | 2:1201 | ||
| 8.2. Dysdifferentiation | 2:1202 | ||
| 8.3. Oxidative Stress | 2:1203 | ||
| 8.4. Redox Regulation and Oxidative Stress Homeostasis | 2:1205 | ||
| 8.5. Longevity Determinant Genes | 2:1208 | ||
| 9. Future Studies and Applications | 2:1211 | ||
| 10. Summary and Conclusion Highlights | 2:1213 | ||
| Note Added in Proof | 2:1217 | ||
| References | 2:1217 | ||
| 65 The Genetics of Yeast Aging: Pathways and Processes | 2:1236 | ||
| 1. Introduction | 2:1237 | ||
| 2. Phenomenology of Aging | 2:1237 | ||
| 3. Genes, Pathways, and Processes | 2:1238 | ||
| 4. RAS2, a Homeostatic Device in Yeast Longevity | 2:1240 | ||
| 5. Caloric Restriction in Yeast | 2:1241 | ||
| 6. A Metabolic Continuum | 2:1242 | ||
| 7. Conclusions | 2:1242 | ||
| Acknowledgments | 2:1243 | ||
| References | 2:1243 | ||
| 66 Oxidative Stress and Longevity Determinant Genes of Drosophila | 2:1246 | ||
| 1. Introduction | 2:1247 | ||
| 2. Relationship between Stress and Longevity | 2:1247 | ||
| 3. Data from Candidate Gene Experiments | 2:1248 | ||
| 3.1. CuZnSOD, MnSOD and Catalase | 2:1248 | ||
| 3.2. Other Genes | 2:1250 | ||
| 4. Data from Genome-Wide Analysis | 2:1251 | ||
| 5. Data Implicating the Role of Mitochondria | 2:1253 | ||
| 6. Discussion | 2:1254 | ||
| 6.1. Quality of the Evidence | 2:1254 | ||
| 6.2. Implications of Tissue-Specific Age Failure | 2:1255 | ||
| 7. Conclusion and Summary Hypothesis | 2:1255 | ||
| Acknowledgments | 2:1256 | ||
| References | 2:1256 | ||
| SECTION 11 Longevity Determinant Genes and Oxidative Stress | 2:1261 | ||
| 67 Toward a Unified Theory of Aging — What Mammals Can Learn from Worms and Other Ephemeral Creatures | 2:1263 | ||
| 1. Summary | 2:1264 | ||
| 2. Theories of Aging | 2:1264 | ||
| 2.1. Programmed Aging Theories | 2:1264 | ||
| 2.2. Stochastic Error Accumulation | 2:1265 | ||
| 3. Oxidative Damage and Senescence | 2:1266 | ||
| 3.1. Evidence from Insects | 2:1267 | ||
| 3.2. Evidence from Worms | 2:1267 | ||
| 3.3. Beyond Oxygen: The Nitrogen Connection | 2:1269 | ||
| 3.4. Still to be Assigned | 2:1269 | ||
| 4. Stress Response and Aging | 2:1270 | ||
| 5. An Emerging Synthesis — With Gaps | 2:1270 | ||
| 5.1. Repair — The End is Near | 2:1271 | ||
| 6. Positional Mapping of Natural Gene Variations Controlling Longevity | 2:1272 | ||
| 7. Conclusions and Prospects | 2:1273 | ||
| Acknowledgments | 2:1274 | ||
| References | 2:1274 | ||
| 68 Mouse Models and Longevity | 2:1284 | ||
| 1. Summary | 2:1285 | ||
| 2. The Aging Process in Mice | 2:1285 | ||
| 3. Mouse Models of Longevity | 2:1286 | ||
| 4. Murine Reverse Genetics and Aging Research | 2:1286 | ||
| 5. The p66shcA Protein | 2:1288 | ||
| 6. The Ablation of p66shcA Increases Lifespan in Mice | 2:1290 | ||
| 7. Mammalian Aging Inducer Genes | 2:1290 | ||
| 8. Conclusions | 2:1291 | ||
| References | 2:1292 | ||
| 69 Oxidative Stress, DNA Repair and Centenarian Survival | 2:1299 | ||
| 1. Introduction | 2:1300 | ||
| 2. The Mitochondrial Fountain of Youth | 2:1301 | ||
| 3. Centenarians Overcome Degeneration of the DNA Repair Process | 2:1303 | ||
| 4. Tumor Suppressors or \"Longevity Promoters | 2:1305 | ||
| 5. Conclusion | 2:1306 | ||
| Acknowledgments | 2:1307 | ||
| References | 2:1308 | ||
| SECTION 12 Non-Invasive Assessment of Oxidative Stress and Therapeutic Intervention | 2:1311 | ||
| 70 Strategies for Controlling Oxidative Stress: Protection Against Peroxynitrite and Hydroperoxides by Selenoproteins and Selenoorganic Compounds | 2:1313 | ||
| 1. Introduction | 2:1314 | ||
| 2. Glutathione Peroxidase and Oxidant Interception Reactions | 2:1314 | ||
| 3. Peroxynitrite, Oxidative Stress and Aging | 2:1315 | ||
| 4. Protection Against Peroxynitrite by Organoselenium Compounds | 2:1316 | ||
| 4.1. Ebselen | 2:1316 | ||
| 4.2. Selenomethionine | 2:1317 | ||
| 5. Protection Against Peroxynitrite by Selenoproteins | 2:1317 | ||
| 5.1. Glutathione Peroxidase | 2:1317 | ||
| 5.2. Selenoprotein P | 2:1318 | ||
| 5.3. Thioredoxin Reductase | 2:1318 | ||
| 6. Potential Protection Against Aging by Pharmacologic/ Nutritive Supplementation with Organoselenium Compounds | 2:1318 | ||
| 6.1. Ebselen and Other GPx Mimics | 2:1318 | ||
| 6.2. Selenium Supplementation | 2:1319 | ||
| Acknowledgments | 2:1319 | ||
| References | 2:1319 | ||
| 71 Salen Manganese Complexes, Combined Superoxide Dismutase/Catalase Mimetics, Demonstrate Potential for Treating Neurodegenerative and Other Age-Associated Diseases | 2:1324 | ||
| 1. Summary | 2:1325 | ||
| 2. Introduction: Reactive Oxygen Species and Disease | 2:1325 | ||
| 3. Synthetic Superoxide Dismutase Mimetics as Potential Therapeutics | 2:1326 | ||
| 4. Salen Manganese Complexes are Catalytic Scavengers of Multiple Types of Reactive Oxygen Species, Providing Advantages Over Superoxide Dismutase | 2:1327 | ||
| 5. EUK-8, a Prototype Salen Manganese Complex with Efficacy in a Broad Range of Disease Models | 2:1328 | ||
| 6. EUK-134, an EUK-8 Analog with Improved Catalase and Cytoprotective Activities In Vitro | 2:1329 | ||
| 7. Salen Manganese Complexes are Neuroprotective In Vivo in Models of Stroke and Seizure-Induced Excitotoxicity | 2:1331 | ||
| 8. Salen Manganese Complexes Rescue a Spongiform Neurodegenerative Disorder Associated with Mitochondrial Oxidative Stress in Mice Lacking MnSOD | 2:1334 | ||
| 9. Salen Manganese Complexes Extend Lifespan of a Multicellular Organism | 2:1337 | ||
| 10. Conclusions | 2:1338 | ||
| Acknowledgments | 2:1338 | ||
| References | 2:1339 | ||
| 72 Glutathione Peroxidase Mimics | 2:1344 | ||
| 1. Summary | 2:1345 | ||
| 2. Role of Glutathione Peroxidase (GPx) and Rationale for Therapeutic Use of GPx Mimics | 2:1345 | ||
| 3. Ebselen | 2:1346 | ||
| 4. BXT-51072 | 2:1347 | ||
| 5. Conclusion | 2:1350 | ||
| References | 2:1350 | ||
| 73 Nutritional Approaches to Reducing Oxidative Stress | 2:1352 | ||
| 1. Summary | 2:1353 | ||
| 2. The Role of Oxidative Stress in Aging | 2:1353 | ||
| 3. Reducing Oxidative Stress — Lowering Exposure to Environmental Oxidants | 2:1354 | ||
| 4. Reducing Oxidative Stress — Lower the In Vivo Generation of Oxidative Free Radicals | 2:1355 | ||
| 5. Reducing Oxidative Stress — Increase the In Vivo Levels of Antioxidant Defenses | 2:1355 | ||
| 6. Clinical Trials on Nutritional Supplements that May Reduce Oxidative Stress | 2:1357 | ||
| 7. Extending Lifespan by Lowering Insulin and Glucose Levels | 2:1359 | ||
| 8. Dietary Changes and Nutritional Supplements that Counteract Age-Related Diseases | 2:1359 | ||
| 9. Conclusions | 2:1360 | ||
| References | 2:1360 | ||
| 74 UV-DNA Repair Enzymes in Liposomes | 2:1368 | ||
| 1. Introduction: What is Aging | 2:1369 | ||
| 2. The Molecular Genetics of Longevity: Telomerase and DNA Repair | 2:1370 | ||
| 3. The Spiral of Life: Aging and Photoaging | 2:1370 | ||
| 4. UV-DNA Repair Enzymes in Liposomes | 2:1372 | ||
| 4.1. Engineering DNA Repair in Skin | 2:1372 | ||
| 4.2. Repair of DNA Damage | 2:1373 | ||
| 4.3. Protection from UV Immunosuppression | 2:1373 | ||
| 4.4. Clinical Testing | 2:1373 | ||
| 5. Commercial Challenges and Opportunities in Anti-Aging Medicine | 2:1374 | ||
| 6. Conclusion | 2:1374 | ||
| Acknowledgments | 2:1374 | ||
| References | 2:1375 | ||
| 75 Mitochondrial Dysfunction in Aging and Disease: Development of Therapeutic Strategies | 2:1377 | ||
| 1. Summary | 2:1378 | ||
| 2. Introduction | 2:1378 | ||
| 3. Opportunities for Mitochondrial Therapeutics | 2:1379 | ||
| 3.1. Mitochondrial Permeability Transition and Radical Production | 2:1381 | ||
| 3.2. Antioxidants as Mitochondrial Therapeutics | 2:1382 | ||
| 3.3. Functional Screening Based on Mitochondrial Membrane Potential | 2:1384 | ||
| Acknowledgments | 2:1388 | ||
| References | 2:1388 | ||
| 76 Nitric Oxide-Blocking Therapeutics | 2:1393 | ||
| 1. Summary | 2:1394 | ||
| 2. NO and NO-Regulating Therapeutics | 2:1394 | ||
| 3. Dithiocarbamate Molecules as NO-Blocking Agents | 2:1395 | ||
| 4. Dual Anti-Inflammatory Activities of Dithiocarbamates | 2:1397 | ||
| 5. Selected Animal Studies of NOX-100 | 2:1397 | ||
| 5.1. Restoration of Blood Pressure in Septic Shock | 2:1397 | ||
| 5.2. Prevention of Bacterial Translocation During Endotoxemia | 2:1398 | ||
| 5.3. Reduction of Inflammatory Gene Expression During Hemorrhagic Shock | 2:1400 | ||
| 6. Clinical Studies of Dithiocarbamate Nitric Oxide-Blockers | 2:1400 | ||
| 7. Conclusion | 2:1400 | ||
| References | 2:1401 | ||
| 77 Nitric Oxide and Mammalian Aging: \"Surplus\" and \"Deficit\" as the Two Faces of a Pharmaceutical Currency for Nitric Oxide-Modulator Drugs | 2:1404 | ||
| 1. Nitric Oxide (NO) Physiological Chemistry Defines the Therapeutic Potential of NO Modulation | 2:1405 | ||
| 2. NO Modulation as a Therapeutic Intervention in Age-Related Diseases | 2:1407 | ||
| 3. \"NO-Enhanced\" Medicines: An Approach to NO Augmentation | 2:1407 | ||
| 4. NO-Enhanced Medicines for Male Erectile Dysfunction (MED) | 2:1408 | ||
| 5. NO-Enhanced Medicines for Drug-Induced Gastrointestinal (GI) Damage | 2:1410 | ||
| 6. Considerations Regarding the Development and Clinical Application of NO-Modulator Drugs | 2:1411 | ||
| Acknowledgments | 2:1412 | ||
| References | 2:1412 | ||
| 78 Genechips for Age/Stress-Related Gene Expression and Analysis | 2:1418 | ||
| 1. Introduction | 2:1419 | ||
| 2. Method for Measuring Oxidative Stress and Age-Related Genes | 2:1419 | ||
| 3. DNA Microarrays | 2:1420 | ||
| 4. Gene Expression of Cells Exposed to Hydrogen Peroxide | 2:1422 | ||
| 5. Concluding Remarks | 2:1426 | ||
| References | 2:1427 | ||
| SECTION 13 Future Trends in Health Care | 2:1431 | ||
| 79 Preventive Medicine and Health Care Reimbursement: A Necessary but Not Sufficient Condition for Wider Access to Preventive Health Services | 2:1433 | ||
| 1. Introduction | 2:1434 | ||
| 2. Consequences of Increasing Human Life Span | 2:1435 | ||
| 3. Technologies for Age-Related Diseases | 2:1437 | ||
| 4. Preventive Medicine, Cardiovascular Disease, and Screening | 2:1438 | ||
| 5. Baby-Boomers Leading the Charge for Health Care Reimbursement | 2:1443 | ||
| 6. Barriers to the Implementation of Preventive Diagnostics and Therapeutics | 2:1444 | ||
| 7. Conclusion | 2:1450 | ||
| Acknowledgments | 2:1450 | ||
| References | 2:1450 | ||
| 80 Tissue Engineering | 2:1458 | ||
| 1. Introduction | 2:1459 | ||
| 2. Tissue Engineering | 2:1459 | ||
| 3. Tissue Engineering of Liver | 2:1460 | ||
| 4. Tissue Engineering of Cardiovascular Tissue | 2:1463 | ||
| 5. Tissue Engineering of Cartilage | 2:1464 | ||
| 6. Conclusion | 2:1465 | ||
| References | 2:1465 | ||
| 81 Database Analysis of Human Intervention Studies (The Kronos Longitudinal Study of Aging and Anti-aging Interventions) | 2:1472 | ||
| 1. Introduction | 2:1473 | ||
| 2. Physiological Reserve Capacity | 2:1474 | ||
| 3. Clinical Interventions | 2:1476 | ||
| 3.1. Remedial Medicine — Diagnose and Treat | 2:1476 | ||
| 3.2. Preventive Medicine — Assess and Intervene | 2:1477 | ||
| 4. General Clinical Guidelines | 2:1478 | ||
| 5. Step 1 — Baseline Data | 2:1478 | ||
| 6. Step 2 — Interventions | 2:1487 | ||
| 6.1. Dietary Supplementation | 2:1488 | ||
| 6.2. Hormone Replacement | 2:1489 | ||
| 6.3. Diet (Optimum Nutrition) | 2:1489 | ||
| 6.4. Exercise | 2:1490 | ||
| 6.5. Pharmaceuticals | 2:1490 | ||
| 7. Step 3 — Ongoing Monitoring | 2:1490 | ||
| 8. Conclusion | 2:1491 | ||
| Acknowledgments | 2:1491 | ||
| References | 2:1492 | ||
| 82 Funding Trends and Possibilities in Oxidative Stress and Aging Research | 2:1494 | ||
| 1. Introduction | 2:1495 | ||
| 2. Funding Sources | 2:1495 | ||
| 3. Conclusion | 2:1498 | ||
| References | 2:1499 | ||
| SECTION 14 Human Life Extension | 2:1501 | ||
| 83 The Ethics of Longevity: Should We Extend the Healthy Maximum Lifespan | 2:1503 | ||
| 1. Introduction | 2:1504 | ||
| 2. Defining the Issue | 2:1504 | ||
| 3. The Ethics of Caring, the Ethics of Choice | 2:1505 | ||
| 4. Scylla and Charybdis | 2:1506 | ||
| 5. Suffering | 2:1507 | ||
| 6. Social Implications | 2:1508 | ||
| 7. Unintended Consequences | 2:1510 | ||
| 8. Summary | 2:1511 | ||
| References | 2:1511 | ||
| 84 Advisability of Human Life Span Extension: Economic Considerations | 2:1513 | ||
| 1. Introduction | 2:1514 | ||
| 2. Aging, Technology, and Health Care Infrastructure | 2:1514 | ||
| 3. America's Elderly Population | 2:1515 | ||
| 4. Declining Earnings Power/Increase in Utilization of Health Care | 2:1517 | ||
| 5. The Economic Attributes of Health Care | 2:1518 | ||
| 6. Public versus Private Provisions | 2:1519 | ||
| 7. Mortality, Work, and Retirement | 2:1520 | ||
| 8. Concluding Remarks | 2:1521 | ||
| References | 2:1521 | ||
| Index | I:1 |