Critical Reviews of Oxidative Stress and Aging

The following sections are included:

• Acknowledgements

• Preface

• List of Contributors

• Contents

The following sections are included:

• Introduction

• Metabolic Rate and Lifespan (Rubner's Metabolic Potential)

• The Rate of Living Theory

• The Free Radical Theory of Aging

• Free Radicals, Damage and Aging

• The Oxidant/Antioxidant Equilibrium

• Active Oxygen and Signal Transduction

• Summary

• References

The following sections are included:

• Summary

• Choice of Spin Trap

• Superoxide

• Hydroxyl Radical

• In Vivo Hydroxyl Radical Detection

• In Vivo and In Vitro Superoxide

• DTPA, EDTA, and Desferal

• References

The following sections are included:

• Introduction: Alkyl Radicals to Oxyradicals — The Oxygen Effect

• Lifetimes and Diffusion of Oxyradicals

• Relative Reactivities of Peroxyl and Alkoxyl Radicals

• Methods for the Generation of Peroxyl and Alkoxyl Radicals

• Peroxyl and Alkoxyl Radical Mediated DNA Strand Breaks

• DNA Base Modifications by Peroxyl and Alkoxyl Radicals

• Conclusions

• Acknowledgment

• References

The following sections are included:

• Introduction

• Why Do Tissues Produce Oxidants?

• Nitric Oxide

• Why is Nitric Oxide Used as an Intercellular Messenger?

• The Limited Reactivity of Nitric Oxide In Vivo

• Nitrogen Dioxide

• Peroxynitrite

• Nitrative versus Nitrosative Stress

• Tyrosine Nitration

• Alternative Mechanisms of Nitration

• Proteins Susceptible to Nitration

• Nitration of Prostacyclin Synthase

• Nitration of Structural Proteins

• Resistance to Viral Infections

• Ageing, Nitrative Stress and the Central Nervous System

• Conclusions

• Abbreviations Used

• References

The following sections are included:

• Summary

• Introduction

• TRX and Its Related Molecules

• TRX Binding Proteins

• Redox Regulation of Transcription Factors by TRX

• Redox Regulation of Apoptosis by TRX

• Cytoprotective Effects of TRX

• Aging and TRX Overexpressing Transgenic Mice

• Oxidative Stress and Central Nervous System

• Conclusion

• References

The following sections are included:

• Introduction

• The Thioredoxin System

• The Glutaredoxin System

• Redox Regulation by Thioredoxin and Glutaredoxin

• Effects of Oxidants and Antioxidants

• Future Perspectives

• Acknowledgments

• References

The following sections are included:

• Introduction

• Source of ROS as Signaling Molecules

• Mechanism of Oxidant Signaling

• Transcription Factor AP-1 and Its Redox Regulation

• Transcription Factor NF-κB and Its Redox Regulation

• Redox-Mediated Intervention in NF-κB Associated Diseases

• Conclusion

• Acknowledgment

• References

The following sections are included:

• Aging is Our #1 Health Problem

• Degenerative Effects of Aging are Universal

• Why do Humans Live So Long? It is in Our Genes

• What is Oxidative Stress?

• Measuring Oxidative Damage
  • Alkenals
  • Hydroperoxides (Aqueous)
  • Hydroperoxides (Lipid)
  • 8-Hydroxydeoxyguanosine (8-OHdG)
  • 8-Epi-Prostaglandin F2α (8-epi-PGF2α)(Isoprostane)
  • Urine Creatinine

• Measuring Prooxidants
  • Antimony
  • Arsenic
  • C-Reactive Protein
  • Cadmium
  • Chromium
  • Chlorine
  • Iron
  • Ferritin
  • Copper
  • Homocysteine
  • Lead
  • Manganese
  • Mercury
  • Nickel

• Measuring Total Antioxidant Capacity
  • Lipid Peroxidation Inhibition Capacity (LPIC)* Assay
  • Oxygen Radical Absorption Capacity (ORAC) Assay
  • ORAC (Aqueous Soluble)
  • ORAC (Lipid Soluble)

• Measuring Primary Antioxidants
  • Available Iron Binding Capacity (AIBC)
  • % Iron Saturation (Total Iron/TIBC)*100%
  • Ceruloplasmin

• Measuring Secondary Antioxidants

• Aqueous Soluble Antioxidants
  • Ascorbic Acid (vitamin C)
  • Bilirubin (Conjugated and Total)
  • Thiols
  • Uric Acid

• Lipid Soluble Antioxidants
  • α-Carotene
  • β-Carotene
  • β-Cryptoxanthin
  • Lutein
  • Lycopene
  • Retinol (vitamin A)
  • Retinyl Palmitate
  • α-Tocopherol (vitamin E)
  • δ-Tocopherol (vitamin E)
  • γ-Tocopherol (vitamin E)
  • Tocopherols/(Chol. + Trig.)
  • Ubiquinol (Coenzyme Q10)
  • Zeaxanthin

• Antioxidant Supporting Factors
  • Albumin
  • Total Protein
  • Albumin/Globulins Ratio
  • Magnesium
  • Selenium
  • Sulfur
  • Zinc

• Clinical Interpretation and Use of Oxidative Stress Biomarkers for Metabolic Optimization

• References

The following sections are included:

• Introduction

• Mechanisms of Oxidative Damage to DNA

• Measurement of Oxidative Damage to DNA
  • Gas Chromatography/Mass Spectrometry
  • LC/MS/MS and LC/MS

• Conclusions

• Acknowledgment

• References

The following sections are included:

• Introduction

• Principle of the HPLC-MS/MS Method
  • HPLC/MS Interface
  • Detection of the Ions

• Measurement of Oxidized Bases within DNA
  • Set-Up of the Assay for Oxidized Bases
  • Gamma and UV Laser Irradiation of Isolated DNA
  • Degradation of Cellular DNA by Gamma Radiation

• Detection of Tandem Lesions within DNA
  • Detection of Formamido/8-oxoGua within DNA
  • Mechanistic Studies

• Conclusion

• References

The following sections are included:

• Introduction

• Measurement Technologies

• GCMS

• Postlabeling

• HPLC/EC

• Column Switching HPLC/EC Method

• Conclusions

• References

The following sections are included:

• Introduction

• Preparation of Samples

• Measurement of 8-OH-Gua

• Endonuclease Nicking Assay

• Measurement of OGG1 mRNA Level

• 8-Hydroxyguanine in Human Leukocyte DNA and Physical Exercise

• 8-Hydroxyguanine, Its Repair Activity, and Rat OGG1 mRNA Induction in the Lungs of Rats Treated with Diesel Exhaust Particles

• Discussion

• References

The following sections are included:

• Introduction

• Principles for HPLC and GC Separation
  • Electrochemical Detection (ECD)
  • Mass Spectrometric Detection (MS)
  • Immunological Methods

• Comparison of Different Methods

• Interpretation of Tissue Levels and Urinary Excretion

• What is Known from Human Studies of Biomarkers of Oxidative DNA Damage?

• Proper Design of Human Intervention Studies

• Future Perspectives

• Conclusions

• References

The following sections are included:

• Introduction

• Methods for Genomic DNA Sequencing

• LMPCR for the Detection of DNA Adducts in Mammalian Cells at Nucleotide Resolution

• Evolution of LMPCR Technology

• Terminal Transferase-Dependent PCR (TDPCR)

• Oxidative Base Damage at Nucleotide Resolution in Normal Human Cells

• Future Developments in Detection of Damage at Nucleotide Resolution

• Conclusion

• Acknowledgments

• References

The following sections are included:

• Introduction

• Antibodies to Oxidation Products of DNA
  • 5-hydroxymethyldeoxyuridine (5-HMdU)
  • 5,6-dihydroxy-5,6-dihydrothymine (Thymine glycol)
  • 8-oxo-2′-deoxyadenosine (8-oxodA)
  • 8,5′-cycloadenosine-5′-monophosphate (8,5′-cyclo-AMP)
  • 8-oxo-2′deoxyguanosine (8-oxodG)

• Pitfalls and Problems of Antibody Production

• Benefits of the Immuno-Approach

• Conclusions

• Acknowledgments

• References

The following sections are included:

• Introduction

• Detection of 8-oxo-2′-deoxyguanosine

• Detection of Oxidative Pyrimidine Lesions

• Detection of Oxidative “Bulky” Lesions

• The Snake Venom Phosphodiesterase Method

• Conclusions

• Acknowledgments

• References

The following sections are included:

• Introduction
  • Background
  • The Principle of the Comet Assay

• Method
  • Cell Isolation
  • Lysis
  • Enzyme Treatment
  • Alkaline Unwinding and Electrophoresis
  • Neutralizing and Staining

• Oxidative DNA Damage and the Impact of Nutrition
  • Molecular Epidemiology
  • In Vitro Cell Studies

• Future Applications and Conclusions

• Conclusion

• Acknowledgments

• References

The following sections are included:

• Introduction

• Protein Carbonyl Assays Using the Spectrophotometric Method

• Protein Carbonyl Assays Using the Immunological Method

• Other Assays for Assessing Protein Oxidation

• Summary

• References

The following sections are included:

• Summary

• Introduction

• Oxidative Stress Parameter Levels in Young Rats Treated with CH and During Aging

• The Step of Protein Synthesis Most Affected by CH Treatment and Aging
  • Effect of CH-treatment and Aging on Polypeptide Chain Completion Time (Tc)
  • Effect of CH-treatment and Aging on Hepatic Polyribosomal Profiles

• Mechanism Underlying the Alterations in the Elongation Step in CH-treated and Old Rats: Modifications in EF-2
  • 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
  • Effect of CH-treatment and Aging on State of Fragmentation of EF-2

• Conclusions

• Acknowledgements

• References

The following sections are included:

• Introduction

• Chemistry of Protein Oxidation

• Protein Oxidation as a Physiological Process

• Protein Oxidation in Diseases

• Accumulation of Oxidatively Modified Proteins in Aging

• Physical Exercise and Oxidative Stress

• Degradation of Oxidized Proteins

• Conclusion

• References

The following sections are included:

• Introduction

• Technology Platform (SELDI TOF-MS)

• Preliminary Studies

• Conclusions/Future Directions

• Acknowledgments

• References

The following sections are included:

• Introduction

• Mechanism of Formation of the Isoprostanes

• Quantification of F₂-Isoprostanes

• Isoprostane Formation In Vivo

• Measurement of the Major Urinary Metabolite of 15-F_2t-Isop as an Index of Systemic Oxidant Status

• Formation of Isoprostanes in Animal Models of Oxidant Stress

• Quantification of F₂-Isops in Association with Human Disease-Studies in Patients with Alzheimer's Disease

• Conclusions

• Acknowledgments

• References

The following sections are included:

• Introduction

• Principles of Electrospray Mass Spectrometry (ESMS)

• Analysis of Phospholipids in Biological Samples

• Detection of Phospholipid Peroxidation in Model Lipid Systems

• Halogenated Lipid Oxidation Products Detected by ESMS

• Lipid Peroxidation Products Observed in Biological and Clinical Samples

• Quantitation in ESMS

• Conclusions

• Abbreviations

• Acknowledgments

• References

The following sections are included:

• Introduction

• Chemical Pathways of the Maillard Reaction In Vivo

• Metal- and Non-Metal Catalyzed Oxidation During Protein Glycation
  • Glucose Autoxidation and Glycoxidation
  • Metal-Binding and Free Radical Generation by Glycated Proteins
  • Carboxymethyl-Lysine: A Molecular “Sink” of the Aging Process
  • Non-Metal Catalyzed Generation of Free Radicals

• Induction of Cellular Oxidative Stress by Advanced Glycation Endproducts
  • RAGE Activation, Oxidative Stress and NF-κB Activation
  • Methylglyoxal Modification of Albumin and Cellular Oxidative Stress

• Advanced Glycation Products as Markers of Longevity

• Conclusions

• Acknowledgments

• References

The following sections are included:

• Scope of This Review

• Origins of the Mitochondrial DNA Theory of Aging

• Elaborations Founded on Implausible Population Dynamics

• Clonal Expansion of Mutant mtDNA

• Clonal Expansion Challenges the “Tip of the Iceberg” Theory

• Once you have Eliminated the Impossible …

• References

The following sections are included:

• Introduction

• Mitochondria Perform Multiple Cellular Functions

• Mitochondrial DNA is Maternally Inherited

• Mitochondrial DNA is Susceptible to Oxidative Damage

• Oxidative Damage to Mitochondrial DNA and Its Repair

• Mitochondrial Damage Checkpoint: Monitoring the Functional State of Mitochondria

• mtDNA Mutations and Aging

• mtDNA Mutations and Mitochondrial Diseases

• mtDNA Mutations and Cancer

• Perspective

• Acknowledgment

• References

The following sections are included:

• Introduction

• Measuring Oxidative DNA Damage
  • Different Analytical Approaches
  • The Range of Values of 8-oxoguanine in Human Cells
  • Reasons for the Discrepancies in Measurement of 8-oxoguanine
  • The ESCODD Approach
  • Optimizing 8-oxoguanine Estimation; What do We Know So Far?
  • How Do the Different Approaches Compare?

• Conclusions

• Acknowledgments

• References

The following sections are included:

• Introduction

• Assessment of Antioxidant Intake And Status
  • Vitamin E
  • Carotenoids
  • Vitamin C
  • Phenolic Antioxidants

• Biomarkers of Oxidative Stress Status
  • Biomarkers of Lipid Oxidation
  • Biomarkers of Protein Oxidation
  • Biomarkers of DNA Oxidation

• Standards of Evidence

• Hierarchy of Research Designs

• Conclusion

• References

The following sections are included:

• Introduction

• Oxidative Stress and the Brain

• Flavonoids as Free Radical Scavengers

• Biological Properties Independent of Free Radical Scavenging

• Biotransformation of Flavonoids

• Interactions of Flavonoids with Cells Derived from the CNS

• Mechanisms of Lipid Peroxide-Induced Neuronal Dysfunction Involving Mitogen Activated Kinases

• Acknowledgments

• References

The following sections are included:

• Introduction

• Phytochemicals in Fruits and Vegetables

• Fruits and Vegetables: Antioxidants and Anti-Inflammatories
  • Spinach and Strawberries
  • Blueberries
  • Aged Garlic Extract
  • Red Bell Pepper
  • Tomatoes

• Beverages: Antioxidants and Anti-Inflammatories
  • Wine
  • Tea

• Conclusions

• Acknowledgments

• References

The following sections are included:

• Introduction

• Inhibition of Lipid Peroxidation by Antioxidant

• Reactivity of the Antioxidant Toward Radicals

• Fate of Antioxidant-Derived Radical

• Location of Antioxidant

• Interactions between Antioxidants

• Pro-Oxidant Action of Antioxidant

• Metabolites

• Concluding Remarks

• References

The following sections are included:

• Introduction

• Uptake and Transport

• Vitamin E Deficiency

• Non-Antioxidant Molecular Mechanisms

• Protein Kinase C Regulation
  • Inhibition by α-Tocopherol is not Caused by a Direct Interaction with Protein Kinase C
  • α-Tocopherol Inhibits Protein Kinase C Phosphorylation-State and Activity, not Expression
  • Effect on Gene Expression

• Effects of Tocopherols on Cell Proliferation

• Conclusions

• Acknowledgments

• References

The following sections are included:

• Introduction

• Bio-Availability and Bio-Activity

• Absorption and Metabolism

• Biochemistry of γT

• Non-Antioxidant Activity

• γT and Coronary Heart Disease

• Summary

• Acknowledgments

• References

The following sections are included:

• Introduction

• Recommendations on Maximum Intake

• Metabolism of Ascorbic Acid

• Properties

• Adverse Effects

• Ascorbic Acid — Antioxidant or Pro-Oxidant

• Ascorbic Acid Intervention

• Measuring Oxidative Damage to DNA

• Urine and Serum Levels of 8-oxo-dG

• Ascorbic Acid and DNA Repair

• Redox Regulation of AP-1

• AP-1 Binding and DNA Repair

• Conclusions

• Acknowledgments

• References

The following sections are included:

• Introduction

• Carotenoids as Antioxidants
  • In vitro Studies
  • Ex vivo Studies
  • In vivo Studies

• Carotenoids as Pro-Oxidants

• Carotenoids and Aging

• Summary

• References

The following sections are included:

• Introduction

• Definition of Functional Foods

• Definition of Food for Specific Health Use (FOSHU)

• Case of “Functional Foods” for Prevention of Oxidative Stress

• Dietary Antioxidants as Functional Foods

• Conclusion

• References

The following sections are included:

• Introduction

• Glutathione in Phase II Reaction and Cell Signal Transduction

• Glutathione and Thioredoxin: A “Parallel” Redox Regulation System

• Glutathione: Synthesis, Nutritional Modulation, and Its Clinical Implication

• Glutathione Transferase and Phytochemicals: Implications in Health and Disease

• Summary

• References

The following sections are included:

• Introduction

• French Paradox and Oligomeric Proanthocyanidins (OPC)

• Chemistry of Polyphenols and Oligomeric Proanthocyanidins

• Occurrence of Oligomeric Proanthocyanidins in Food and Beverage

• Dietary Intake and Bioavailability of Oligomeric Proanthocyanidins

• Nutritional Benefits of Oligomeric Proanthocyanidins (OPC)

• Recent Advances in Natural Grape Seed Proanthocyanidin Research
  • Safety of GSPE
  • Free Radical Scavenging Activity
  • Protection Against Drug- and Chemical-Induced Multiorgan Toxicity
  • Cardioprotection
  • Protection Against Stress-Induced Oxidative Gastrointestinal Injury
  • Cancer Chemoprevention
  • Age-Related Hypertension and Glycosylated Hemoglobin Study
  • Improvement of Lipid Profile in Hypercholesterolemic Human Subjects
  • Inflammation, Angiogenesis, SPF and Skin Health
  • Human Pancreatitis Study
  • Mechanistic Pathways of Cytoprotection by GSPE

• Conclusion

• References

The following sections are included:

• Introduction

• Redox Sensitive Transcription Factors

• Nuclear Factor Kappa Binding Protein NF-κB

• Activator Protein 1 (API)

• Vitamin C Effects on Gene Expression in the Vasculature

• Vitamin E Effects on Gene Expression in the Vasculature

• Conclusions

• Acknowledgments

• References

The following sections are included:

• Introduction

• Antioxidant Enzymes and Compounds

• DNA Repair

• Lipid Degradation and Repair

• Protein Degradation

• Adaptive Response

• Conclusions

• Acknowledgments

• References

The following sections are included:

• Introduction

• General Characteristics and Isoforms of Heme Oxygenase

• Functions of the Products of the HO Reaction
  • Carbon Monoxide (CO)
  • Biliverdin and Bilirubin
  • Iron

• Regulation of Expression of HO-1
  • Structure of the HO-1 Gene and Its Promoter and Enhancer Regions

• Anti-Inflammatory and Antioxidant Properties of HO-1

• Heme Oxygenase and Aging

• Acknowledgments

• References

The following sections are included:

• Introduction

• Antioxidant Action of MTs
  • Evidence Obtained from In Vitro Studies
  • Evidence Obtained from Studies Using Cultured Cells
  • Evidence Obtained from Intact Animal Studies
  • Direct Evidence Obtained from Genetically Altered Mouse Models

• Possible Mechanisms of Antioxidant Action of MTs

• MTs and Aging

• Conclusion

• Acknowledgments

• References

The following sections are included:

• Introduction

• DNA Repair Systems

• DNA Polymerases, a Central Role in DNA Repair

• Nucleotide Excision Repair (NER)

• Base Excision Repair (BER)

• Reversal of DNA Damage

• Single-Strand Break Repair

• Double-Strand Break Repair (DSBR)

• Mismatch Repair (MMR)

• Repair of DNA-DNA and Protein-DNA Crosslinks

• DNA Repair Heterogeneity

• Regulation of DNA Repair Genes

• Human DNA Repair Syndromes

• Conclusion

• Acknowledgments

• References

The following sections are included:

• Introduction

• DNA Repair Mechanisms in Mammalian Mitochondria

• Base Excision Repair Pathways in Mitochondria

• DNA Glycosylases in Mammalian Mitochondria
  • UDG1
  • mtODE (Mitochondrial Oxidative Damage Endonuclease)
  • mtTGEndo (Mitochondrial Thymine Glycol Endonuclease)

• Other Mitochondrial Enzymes Involved in DNA Repair
  • DNA Polymerase Gamma
  • AP Endonucleases
  • Damage Reversal
  • Mismatch Repair
  • Recombinational Repair

• Changes in mtDNA Repair with Age

• Perspectives

• Acknowledgment

• References

The following sections are included:

• Introduction

• Reduction of Lipoate to Dihydrolipoate: The Metabolic Antioxidant

• Lipoyl Residues in Oxidative Metabolism

• Redox Properties: Biological Implications
  • NF-κB
  • Acquired Immunodeficiency Syndrome (AIDS)
  • Caspase-Dependent Cell Death
  • Cell Adhesion
  • Reductive Stress
  • Glucose Uptake
  • A Novel Form of Lipoic Acid

• Conclusion

• Acknowledgment

• References

The following sections are included:

• Introduction

• DNA Damage and Repair Systems

• Oxidative DNA Damage and Recovery in DNA of Lymphocytes In Vitro Enriched with Ubiquinol-10 or Ubiquinone-10

• Effect of CoQ₁₀ In Vivo Supplementation on DNA Damage and Its Repair in Primary Cultured Lymphocytes

• Effect of In Vivo CoQ₁₀ Supplementation on DNA Repair Enzyme Expression

• Conclusion

• Acknowledgments

• References

The following sections are included:

• Summary

• Introduction

• Dietary Intake of Antioxidants

• Measurement of Individual Antioxidants

• Total Antioxidant Capacity

• Pitfalls in the Methods of Assessment

• Conclusion

• Acknowledgments

• References

The following sections are included:

• Introduction

• Understanding Cancer

• Epidemiology of Twin Studies

• Rate of Knowledge Expansion in Medicine

• Vitamin Supplements and Cancer Prevention

• Cardiovascular Disease

• Conclusion

• References

The following sections are included:

• Introduction

• Lipid Peroxidation and Antioxidants

• Vitamin E

• Nitric Oxide as an Antioxidant

• Vitamin C

• Antioxidant Network

• Aging

• Summary

• Abbreviations

• References

The following sections are included:

• Summary

• Introduction

• Methods

• Results

• Discussion

• Conclusion

• References

The following sections are included:

• Introduction

• Mitochondrial Injury

• Inflammation

• The Balance between Superoxide and Superoxide Dismutases

• Other Ways of Upsetting the Balance

• SOD Deficiency

• Oxidative Stress and Malignancy

• References

The following sections are included:

• Introduction

• Mechanisms of Atherosclerosis and Cardiovascular Events

• Evidence of Enhanced Oxidative Stress and Increased Novel CVRF in Individuals at High Risk for Cardiovascular Disease

• Conclusion

• References

The following sections are included:

• Introduction

• Oxidative Stress and Cell Pathophysiology

• Animal Models-Induction of Tumors by Oxidants

• Evidence for Role of Oxidative Stress in Human Carcinogenesis

• Conclusions

• References

The following sections are included:

• Introduction

• Light, Oxidation and DNA Damage

• Basal Cell Carcinoma (BCC)

• Genetics

• Oxidative Stress and Apoptosis

• Actinic Keratoses (AK) and Squamous Cell Carcinoma (SCC)

• Treatment

• p53

• Melanoma

• Treatment

• Melanoma and Oxidative Metabolism

• Conclusion

• References

The following sections are included:

• Summary

• Introduction

• Changes in Endogenous Antioxidant Enzyme Activities with Age

• Antioxidant Enzyme Upregulation: Common Properties of Propargylamines

• Variability of an Optimal Dose of (-)Deprenyl on Antioxidant Enzyme Upregulation

• Possible Roles of Upregulation of Antioxidant Enzymes in Life Span Extension of Animals

• Neurohumoral Events Affected by (-)Deprenyl

• Conclusions

• Acknowledgments

• References

The following sections are included:

• Introduction

• Multiple Factors Contribute to AMD

• Oxidative Stress and AMD

• Age-Related Changes of Plasma Antioxidants

• Mitochondria of RPE as a Target of Oxidative Injury

• Protection of RPE by Detoxification Enzyme Inducers

• Conclusion

• Acknowledgments

• References

The following sections are included:

• Introduction

• Antioxidant Levels in Peripheral Blood

• Placental Antioxidant Levels

• Antioxidants and the Treatment of Preeclampsia

• Antioxidants and the Immune System

• Conclusion

• References

The following sections are included:

• Introduction

• Fenton Chemistry and “Free” Iron

• “Free” Iron in the Biological Environment

• Significance of Superoxide in Iron-Dependent Oxidative Damage

• Iron Transporter

• Post-transcriptional Regulation of Iron Metabolism

• Hemochromatosis

• Iron and Carcinogenesis in Humans

• Iron and Carcinogenesis in Animals

• Target Genes of Oxidative Stress-Induced Carcinogenesis

• Conclusion

• Acknowledgments

• References

The following sections are included:

• Summary

• Introduction

• Transgenic/Knockout Mouse Models with Alterations in the Antioxidant Defense System

• Transgenic/Knockout Mouse Models Used to Study the Role of Oxidative Stress in Aging

• Acknowledgments

• References

The following sections are included:

• Introduction

• Extension of Maximum Life-Span

• Attenuation of Oxidative Damage and the Associated Decline in Function

• New Directions in Caloric Restriction Research

• Conclusions

• Acknowledgments

• References

The following sections are included:

• Introduction

• Growth Hormone and IGF-I

• Insulin, Glucose, and Diabetes

• Estrogens

• Thyroid Hormones

• Adrenal Hormones

• Conclusion

• References

The following sections are included:

• Introduction

• Exercise Principles

• Aging Principles

• Pleiotropic and Hormetic Effects of Exercise and Aging

• Exercise-Induced Oxidative Stress

• Exercise as a Prevention Against Oxidative Stress

• Different Exercise Protocols

• Conclusion

• Acknowledgments

• References

The following sections are included:

• The Evolutionary Theory of Senescence

• Comparative Studies of Aging and Longevity

• Evolutionary Basis of Life Extension Through Calorie Restriction

• Evolution of Human Reproductive Senescence

• Evolution of Germ-Line Immortality

• Human Aging and Oxidative Stress

• References

The following sections are included:

• Biology of Human Aging

• Evolutionary and Comparative Biology Studies

• The Genetic Complexity of Aging and Longevity Processes

• What are the Longevity Determinant Genes?

• DNA Oxidative Damage

• Glycation and Glycoxidation

• Genetic Stability, Cancer and the Dysdifferentiation Hypothesis of Aging

• Recent Support from Other Laboratories

• Future Studies and Applications

• Summary and Conclusion Highlights

• Note Added in Proof

• References

The following sections are included:

• Introduction

• Phenomenology of Aging

• Genes, Pathways, and Processes

• RAS2, a Homeostatic Device in Yeast Longevity

• Caloric Restriction in Yeast

• A Metabolic Continuum

• Conclusions

• Acknowledgments

• References

The following sections are included:

• Introduction

• Relationship between Stress and Longevity

• Data from Candidate Gene Experiments

• Data from Genome-Wide Analysis

• Data Implicating the Role of Mitochondria

• Discussion

• Conclusion and Summary Hypothesis

• Acknowledgments

• References

The following sections are included:

• Summary

• Theories of Aging

• Oxidative Damage and Senescence

• Stress Response and Aging

• An Emerging Synthesis — With Gaps

• Positional Mapping of Natural Gene Variations Controlling Longevity

• Conclusions and Prospects

• Acknowledgments

• References

The following sections are included:

• Summary

• The Aging Process in Mice

• Mouse Models of Longevity

• Murine Reverse Genetics and Aging Research

• The p66^shcA Protein

• The Ablation of p66^ShcA Increases Lifespan in Mice

• Mammalian Aging Inducer Genes

• Conclusions

• References

The following sections are included:

• Introduction

• The Mitochondrial Fountain of Youth

• Centenarians Overcome Degeneration of the DNA Repair Process

• Tumor Suppressors or “Longevity Promoters”

• Conclusion

• Acknowledgments

• References

The following sections are included:

• Introduction

• Glutathione Peroxidase and Oxidant Interception Reactions

• Peroxynitrite, Oxidative Stress and Aging

• Protection Against Peroxynitrite by Organoselenium Compounds

• Protection Against Peroxynitrite by Selenoproteins

• Potential Protection Against Aging by Pharmacologic/Nutritive Supplementation with Organoselenium Compounds

• Acknowledgments

• References

The following sections are included:

• Summary

• Introduction: Reactive Oxygen Species and Disease

• Synthetic Superoxide Dismutase Mimetics as Potential Therapeutics

• Salen Manganese Complexes are Catalytic Scavengers of Multiple Types of Reactive Oxygen Species, Providing Advantages Over Superoxide Dismutase

• EUK-8, a Prototype Salen Manganese Complex with Efficacy in a Broad Range of Disease Models

• EUK-134, an EUK-8 Analog with Improved Catalase and Cytoprotective Activities In Vitro

• Salen Manganese Complexes are Neuroprotective In Vivo in Models of Stroke and Seizure-Induced Excitotoxicity

• Salen Manganese Complexes Rescue a Spongiform Neurodegenerative Disorder Associated with Mitochondrial Oxidative Stress in Mice Lacking MnSOD

• Salen Manganese Complexes Extend Lifespan of a Multicellular Organism

• Conclusions

• Acknowledgments

• References

The following sections are included:

• Summary

• Role of Glutathione Peroxidase (GPx) and Rationale for Therapeutic Use of GPx Mimics

• Ebselen

• BXT-51072

• Conclusion

• References

The following sections are included:

• Summary

• The Role of Oxidative Stress in Aging

• Reducing Oxidative Stress — Lowering Exposure to Environmental Oxidants

• Reducing Oxidative Stress — Lower the In Vivo Generation of Oxidative Free Radicals

• Reducing Oxidative Stress — Increase the In Vivo Levels of Antioxidant Defenses

• Clinical Trials on Nutritional Supplements that May Reduce Oxidative Stress

• Extending Lifespan by Lowering Insulin and Glucose Levels

• Dietary Changes and Nutritional Supplements that Counteract

• Age-Related Diseases

• Conclusions

• References

The following sections are included:

• Introduction: What is Aging?

• The Molecular Genetics of Longevity: Telomerase and DNA Repair

• The Spiral of Life: Aging and Photoaging

• UV-DNA Repair Enzymes in Liposomes

• Commercial Challenges and Opportunities in Anti-Aging Medicine

• Conclusion

• Acknowledgments

• References

The following sections are included:

• Summary

• Introduction

• Opportunities for Mitochondrial Therapeutics

• Acknowledgments

• References

The following sections are included:

• Summary

• NO and NO-Regulating Therapeutics

• Dithiocarbamate Molecules as NO-Blocking Agents

• Dual Anti-Inflammatory Activities of Dithiocarbamates

• Selected Animal Studies of NOX-100

• Clinical Studies of Dithiocarbamate Nitric Oxide-Blockers

• Conclusion

• References

The following sections are included:

• Nitric Oxide (NO) Physiological Chemistry Defines the Therapeutic Potential of (NO) Modulation

• (NO) Modulation as a Therapeutic Intervention in Age-Related Diseases

• “(NO)-Enhanced” Medicines: An Approach to (NO) Augmentation

• (NO)-Enhanced Medicines for Male Erectile Dysfunction (MED)

• (NO)-Enhanced Medicines for Drug-Induced Gastrointestinal (GI) Damage

• Considerations Regarding the Development and Clinical Application of (NO)-Modulator Drugs

• Acknowledgments

• References

The following sections are included:

• Introduction

• Method for Measuring Oxidative Stress and Age-Related Genes

• DNA Microarrays

• Gene Expression of Cells Exposed to Hydrogen Peroxide

• Concluding Remarks

• References

The following sections are included:

• Introduction

• Consequences of Increasing Human Life Span

• Technologies for Age-Related Diseases

• Preventive Medicine, Cardiovascular Disease, and Screening

• Baby-Boomers Leading the Charge for Health Care Reimbursement

• Barriers to the Implementation of Preventive Diagnostics and Therapeutics

• Conclusion

• Acknowledgments

• References

The following sections are included:

• Introduction

• Tissue Engineering

• Tissue Engineering of Liver

• Tissue Engineering of Cardiovascular Tissue

• Tissue Engineering of Cartilage

• Conclusion

• References

The following sections are included:

• Introduction

• Physiological Reserve Capacity

• Clinical Interventions

• General Clinical Guidelines

• Step 1 — Baseline Data

• Step 2 — Interventions

• Step 3 — Ongoing Monitoring

• Conclusion

• Acknowledgments

• References

The following sections are included:

• Introduction

• Funding Sources

• Conclusion

• References

The following sections are included:

• Introduction

• Defining the Issue

• The Ethics of Caring, the Ethics of Choice

• Scylla and Charybdis

• Suffering

• Social Implications

• Unintended Consequences

• Summary

• References

The following sections are included:

• Introduction

• Aging, Technology, and Health Care Infrastructure

• America’s Elderly Population

• Declining Earnings Power/Increase in Utilization of Health Care

• The Economic Attributes of Health Care

• Public versus Private Provisions

• Mortality, Work, and Retirement

• Concluding Remarks

• References

The following sections are included:

• Index