Aging and Age-Related Disorders (eBook)

Stephen Bondy, Kenneth Maiese (Herausgeber)

eBook Download: PDF

2010 | 2010
XVI, 472 Seiten
Humana Press (Verlag)
978-1-60761-602-3 (ISBN)

Infos

Features that characterize the aging process include the gradual accumulation of cell damage after prolonged exposure to oxidative and inflammatory events over a lifetime. In addition to the accretion of lesions, the intrinsic levels of pro-oxidant and aberrant immune responses are elevated with age. These adverse events are often further enhanced by the chronic and slow progressing diseases that characterize the senescent brain and cardiovascular system. The incidence of some disorders such as Alzheimer's disease and vascular diseases are sufficiently prevalent in the extreme elderly that these disorders can arguably be considered 'normal'. Aging and Aging-Related Disorders examines the interface between normal and pathological aging, and illustrates how this border can sometimes be diffuse. It explores and illustrates the processes underlying the means by which aging becomes increasingly associated with inappropriate levels of free radical activity and how this can serve as a platform for the progression of age-related diseases. The book provides chapters that examine the interactive relationship between systems in the body that can enhance or sometimes even limit cellular longevity. In addition, specific redox mechanisms in cells are discussed. Another important aspect for aging discussed here is the close relationship between the systems of the body and exposure to environmental influences of oxidative stress that can affect both cellular senescence and a cell's nuclear DNA. What may be even more interesting to note is that these external stressors are not simply confined to illnesses usually associated with aging, but can be evident in maturing and young individuals. A broad range of internationally recognized experts have contributed to this book. Their aim is to successfully highlight emerging knowledge and therapy for the understanding of the basis and development of aging-related disorders.

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Features that characterize the aging process include the gradual accumulation of cell damage after prolonged exposure to oxidative and inflammatory events over a lifetime. In addition to the accretion of lesions, the intrinsic levels of pro-oxidant and aberrant immune responses are elevated with age. These adverse events are often further enhanced by the chronic and slow progressing diseases that characterize the senescent brain and cardiovascular system. The incidence of some disorders such as Alzheimer's disease and vascular diseases are sufficiently prevalent in the extreme elderly that these disorders can arguably be considered "e;normal"e;. Aging and Aging-Related Disorders examines the interface between normal and pathological aging, and illustrates how this border can sometimes be diffuse. It explores and illustrates the processes underlying the means by which aging becomes increasingly associated with inappropriate levels of free radical activity and how this can serve as a platform for the progression of age-related diseases. The book provides chapters that examine the interactive relationship between systems in the body that can enhance or sometimes even limit cellular longevity. In addition, specific redox mechanisms in cells are discussed. Another important aspect for aging discussed here is the close relationship between the systems of the body and exposure to environmental influences of oxidative stress that can affect both cellular senescence and a cell s nuclear DNA. What may be even more interesting to note is that these external stressors are not simply confined to illnesses usually associated with aging, but can be evident in maturing and young individuals. A broad range of internationally recognized experts have contributed to this book. Their aim is to successfully highlight emerging knowledge and therapy for the understanding of the basis and development of aging related disorders.

Inhalt

Preface 5
Contents 7
Contributors 10
Part I General Aspects of Aging 15
Protein Redox-Regulation Mechanisms in Aging 16
1 Introduction 17
2 Postmitotic Aging and Redox Homeostasis 18
3 Redox-Regulation Pathways and Repair of Proteins 21
3.1 General Principles 21
3.2 Intracellular Mechanisms 23
3.2.1 Role of Thiol-Based Repair Systems 23
3.2.2 The Roles of Proteasome, Ubiquitin, and SUMO 24
3.2.3 The Roles of Mitochondrial Antioxidant Systems and of ATP-Dependent Proteases 26
3.3 Extracellular Mechanisms 27
4 Altered Redox-Regulation Pathways and Age-Related Disorders 28
4.1 Role of Thiol-Based Repair Systems 29
4.1.1 In Alzheimer's Disease 30
4.1.2 In Parkinson's Disease 30
4.1.3 In Cataracts 30
4.1.4 In Diabetes 31
4.2 The Roles of Proteasome, Ubiquitin, and SUMO 31
4.2.1 In Alzheimer's Disease 32
4.2.2 In Parkinson's Disease 33
4.2.3 In Cataracts 33
4.2.4 In Diabetes 33
5 Concluding Remarks 34
References 34
Nitrosative Stress in Aging -- Its Importance and Biological Implications in NF-B Signaling 39
1 Introduction 40
1.1 The Oxidative Stress Hypothesis of Aging -- Historical Account 40
1.2 The Concept of Nitrosative Stress 43
2 Reactive Nitrogen Species and Nitrosative Stress 44
2.1 First Come Definitions 44
2.1.1 “Nitrosation” and “Nitrosylation” – It Obviously Needs SomeClarification 44
2.2 Reactive Nitrogen Species -- Chemistry and Availability 45
2.3 Nitrosylation and Nitration Are Mediators of Cell Signaling 46
2.3.1 Nitrosylation 46
2.3.2 Nitration 47
3 NF-B, Aging, and Nitrosative Stress 48
3.1 NF-.B Signaling 48
3.2 NF-.B Signaling Increases in Aging 49
3.3 Nitration of Proteins Increases with Aging -- Tyrosine Nitration 50
3.4 NF-.B Signaling and Skeletal Muscle Atrophy 51
3.5 Loss of Skeletal Muscle in Old Age Is Associated with Increased Nitration of Muscle Proteins and NF- B Activation 52
3.6 Peroxynitrite-Induced Tyrosine Nitration of I B Causes NF- B Activation 53
3.7 Nitration by Peroxynitrite and NF- -- B Activation Is Supported by Proinflammatory Conditions -- Link to Inflamm-aging 54
3.8 Thus, Is NF-.B a Signaling Mediator of Aging? 56
4 Summary and Conclusions 57
References 58
Intervention with Multiple Micronutrients Including Dietaryand Endogenous Antioxidants for Healthy Aging 67
1 Introduction 68
2 Oxidative Stress During Aging 69
3 Oxidative Stress Influencing Mitochondria, Lysosome, and Proteosome Function During Aging 71
4 Oxidative Stress Influencing the Length of Telomere During Aging 72
5 Chronic Inflammation During Aging 73
6 Aging Influencing Immune Function 74
7 Aging Influencing Antioxidant Defense Systems 74
8 Antioxidant Supplementation Influencing Age-Related Functional Deficits 78
9 Rationale for Using Multiple Dietary and Endogenous Antioxidants in Age-Related Functional Deficits 80
10 Changes in Diet and Lifestyle 82
11 Summary and Conclusions 82
References 83
Advanced Glycation End Products, RAGE, and Aging 91
1 Introduction 91
2 AGEs, Oxidant Stress, and Inflammation 92
3 AGE and AGEing Hypothesis 93
3.1 AGEs in Brain 94
3.2 AGE--RAGE, Aging, and the Heart 95
3.3 Nutritional and Therapeutic Approaches to Limit AGEs 96
4 Conclusions 96
References 97
Sirtuins and Mammalian Aging 103
1 Introduction 104
1.1 Aging and Longevity 104
1.2 Sirtuin Function and Longevity 105
2 Sirtuins: Localization, Substrates, and Functions 110
2.1 Sirt1 110
2.2 Sirt2 111
2.3 Sirt3 112
2.4 Sirt4 112
2.5 Sirt5 113
2.6 Sirt6 113
2.7 Sirt7 114
3 Sirtuins in Aging-Related Processes 115
3.1 Immunity, Inflammation, and Aging 115
3.2 Autophagy 115
4 Sirtuins in Aging-Associated Degenerative Diseases 116
4.1 Type 2 Diabetes and Metabolic Syndrome 116
4.2 Alzheimer's Disease 117
4.3 Age-Related Macular Degeneration 118
4.4 Cardiovascular Disease 118
4.5 Stroke 118
4.6 Cancer 119
4.7 Sarcopenia 120
5 Conclusions 121
Glossary 121
References 122
Estrogenic Modulation of Longevity by Inductionof Antioxidant Enzymes 130
1 Mitochondria as Sources and Targets of Age-Associated Damage 131
2 Difference in Oxidative Stress in Aging Expressed a Differential Longevity Between Genders 132
3 Telomerase Is a Longevity-Associated Gene Regulated by Estrogens 134
4 Differential Longevity Between Genders: A Methodological Approach 136
5 Concluding Remarks 137
References 138
Mitochondrial Respiratory Function Decline in Agingand Life-Span Extension by Caloric Restriction 140
1 Introduction 141
2 Mitochondrial Function Decline During the Aging Process 142
2.1 Production of ATP and ROS in Human and Animal Cells 142
2.2 Accumulation of Mitochondrial DNA Mutation in Aged Tissues 142
2.3 Bioenergetic Function Decline of Mitochondria During Aging 144
2.4 Mitochondrial Dysfunction in Age-Related Diseases 147
3 Age-Associated Alterations in Gene Expression and Protein Modification 147
4 The Role of Sirt1 in Life-Span Extension by Caloric Restriction 149
4.1 Sirtuins in the Life-Span--Extending Effect of Caloric Restriction 149
4.2 The Regulation of Mitochondrial Function and Life Span by Sirt1 149
4.3 Other Sirtuins in Regulation of Mitochondrial Function 150
4.4 Therapeutic Agent Targeting Sirtuins in Age-Related Diseases 151
5 Conclusions 151
References 152
Methylglyoxal, Oxidative Stress, and Aging 160
1 Introduction 160
2 Methylglyoxal Metabolism 162
3 Free Radical Theory of Aging 163
4 Methylglyoxal and Oxidative Stress 166
4.1 Methylglyoxal and Superoxide Anion Formation 166
4.2 Methylglyoxal and Hydrogen Peroxide Production 167
4.3 Methylglyoxal and Nitric Oxide/Peroxynitrite Production 167
4.4 Methylglyoxal and p38 MAPK 167
4.5 Methylglyoxal and Activation of NF-B 168
4.6 Methylglyoxal, Antioxidant Enzymes, and Reduced Glutathione 168
5 Methylglyoxal, Oxidative Stress, and Aging 169
6 Prevention of Methylglyoxal-Induced Aging 170
7 Conclusions 171
References 172
Part II The Cardiovascular System 179
Novel Strategies for Neurovascular Longevity During Aging 180
1 Introduction 181
1.1 Aging and Oxidative Stress 181
2 FoxOs 183
2.1 Background, Expression, and Regulation of FoxOs 183
3 Erythropoietin 187
3.1 Background, Structure, and Expression for EPO 187
3.2 Cellular Signaling for EPO and the EPO Receptor 188
4 FoxOs, EPO, and the Control of Cell Injury 189
5 FoxOs, EPO, and the Immune System 190
6 FoxOs, EPO, Stems Cells, and Tissue Development 192
7 FoxOs, EPO, Diabetes, and Metabolic Pathways 194
8 Clinical Strategies and Future Perspectives 197
References 201
Oxidative Stress in Vascular Disease 219
1 Introduction 220
2 Lipoprotein Oxidation in Atherosclerosis 222
3 Oxidants in the Vascular Wall 223
4 Role of Redox Enzymes in Vascular Disease 224
4.1 NADPH Oxidase 224
4.2 Xanthine Oxidase 225
4.3 Endothelial Nitric Oxide Synthase 226
4.4 Myeloperoxidase 226
4.5 Lipoxygenases 226
4.6 Antioxidants 227
5 Role of Reactive Species in Mechanical and Shear Stress 227
6 Role of Mitochondria in Vascular Disease 228
7 Oxidative Stress, Telomere Length, and Senescence 229
8 DNA Damage in Vascular Disease 231
9 Antioxidants and Cardiovascular Diseases 233
10 Conclusions 234
References 235
The Role of Mitochondrial Reactive Oxygen Species Formation for Age-Induced Vascular Dysfunction 244
1 Introduction 244
2 The Cardiovascular System 245
2.1 Vascular Function and Oxidative Stress 246
2.2 The Nitric Oxide/Superoxide System 248
2.3 Cross-Talk Between Mitochondrial and NADPH Oxidase--Generated Reactive Nitrogen and Oxygen Species 249
3 Clinical Background 251
4 Aging 253
4.1 Aging and Oxidative Stress 253
4.2 Aging and Mitochondrial DNA 253
4.3 Aging, Mitochondrial Oxidative Stress, and Endothelial Dysfunction 254
4.4 Futile Counterregulation by Enhanced Gene Expression of Oxidant Defense Mechanisms 255
5 Recent Developments in Aging Concepts 258
6 Perspective 259
References 259
Aging, Oxidative Stress, and Cardiovascular Disorders 265
1 Background 265
2 Free Radical Theory of Aging 266
3 Imbalance Between Oxygen-Derived Free Radicals and Antioxidative Defense in Aging 267
4 Age-Induced Oxidative Stress and Vascular Dysfunction 267
5 Aging-Related Genes: p66Shc 268
6 p66Shc: Role in Aging and Age-Related CardiovascularDiseases 269
7 Aging-Related Gene: Sirt1 272
8 Sirt1: Role in Aging and Age-Related Cardiovascular Diseases 273
9 Environmental Factors Affecting Life Span 274
9.1 Caloric Restriction 274
9.2 Physical Exercise 274
9.3 Antioxidant Treatment 275
9.4 Resveratrol 275
10 Summary and Conclusions 275
References 276
Oxidative Stress, Aging, and Cardiovascular Disease 282
1 Introduction 282
2 Oxidative Stress 283
3 Free Radicals 284
3.1 Production 287
3.2 Damaging Reactions 288
3.3 Defense: Antioxidants 290
4 Free Radicals and Aging 292
5 Oxidative Stress and Cardiovascular Diseases 293
6 Atherosclerosis 294
7 Conclusions 297
References 298
Antioxidation in Prevention of CardiovascularDiseases -- An Effect of Polyphenols 302
1 Introduction 302
2 Catechins Suppress Oxidative Stress in Myocardial Ischemia 304
3 Catechins Suppress Oxidative Stress in Myocarditis 305
4 Catechins Suppress Oxidative Stress in Transplant Rejection 306
5 Summary and Future Direction 307
References 308
Vascular Aging and Oxidative Stress: HormesisINTbreak and Adaptive Cellular Pathways
1 Introduction 314
1.1 Aging: Different Theories of Aging 314
1.2 Cellular Aging or Cellular Senescence 315
1.3 Vascular Endothelial Aging 317
1.4 Hormesis in Aging 319
2 Summary and Conclusions 320
References 321
Role of Oxidative Stress in Mediating Elevated Blood Pressure with Aging 326
1 Introduction 326
2 The Role of Oxidative Stress in Control of Blood Pressure 327
2.1 Blood Pressure, Oxidative Stress, and the Kidney 327
2.2 Sex Differences in Oxidative Stress 329
2.3 Postmenopausal Hypertension 331
3 Studies in Aging Animals Linking Oxidative Stress and Blood Pressure 331
3.1 Studies in Spontaneously Hypertensive Rats 331
3.2 Measurement of Oxidative Stress 332
3.3 Measurement of Antioxidant Enzyme Expression 332
3.4 Functional Studies to Evaluate the Role of Oxidative Stress on Blood Pressure in SHR 333
3.5 Studies to Mimic Endothelial Dysfunction in Aging 335
3.6 Lack of Tools to Study ROS and Blood Pressure Regulation 335
4 Summary and Conclusions 336
References 336
Part III The Nervous System 340
Melatonin, Oxidative Stress, and the Aging Brain 341
1 Introduction 341
1.1 Oxidative Stress and Brain Aging 342
1.2 Inflammation and the Aged Brain 342
1.3 Mitochondrial Dysfunction and Brain Aging 343
2 The Treatment of Chronic Neurodegenerative Disorders 344
2.1 The Potential Retardation of Brain Aging by Melatonin 345
2.1.1 Melatonin and Overall Phenotypic Aging 346
2.1.2 Specific Effects of Melatonin on Events Relating to Brain Aging 346
2.1.3 The Potential for Melatonin Treatment of Specific Neurologic Disease 346
3 Processes That May Underlie the Ability of Melatonin to Modulate the Aging Process 347
3.1 Melatonin as an Antioxidant 347
3.2 The Role of Melatonin in the Regulation of Immune Function 348
3.3 Melatonin Receptors and Enzyme Induction 348
3.4 The Link Between Aging and Circadian Events 349
3.5 Melatonin and Mitochondria 350
3.6 Summary of Mechanisms of Melatonin Action and Suggestions for Future Work 350
4 Conclusions 351
References 352
The SAM Strain of Mice, a Higher Oxidative Stress,Age-Dependent Degenerative Disease, and SenescenceAcceleration Model 360
1 The SAM Strain of Mice Is a Unique Model for Senescence Acceleration 361
1.1 A Brief History of the Development of SAM Strains of Mice -- A Mechanism to Generate Mice 361
1.2 Accelerated Senescence and SAM Mice 362
2 The SAM Strain of Mice Is a Unique Model for Several Age-Dependent Disorders 363
2.1 The SAM Strain of Mice Is a Model for Age-Associated Disorders 364
2.2 Age-Dependent Degenerative Change of Tissues in SAMP Mice 365
3 SAMP Strains of Mice Show a Higher Oxidative Stress Status as a Unique Biological Characteristic 366
3.1 A Higher Oxidative Stress Status is a Primary Characteristic of SAMP Strains of Mice 366
3.2 Mitochondrial Dysfunction Is Observed in SAMP Mice 367
3.3 A Higher Oxidative Stress Status Is a Possible Cause of Senescence Acceleration and Degeneration of Cells in SAMP Mice 369
4 Interventions of Mitochondrial Dysfunction, Senescence Acceleration, and Age-Dependent Disorders 371
4.1 Interventions of Senescence Acceleration and Age-Dependent Disorders 371
4.2 Improvements in Mitochondrial Dysfunction 372
5 Conclusions 373
References 373
Antioxidants Combined with Behavioral Enrichment Can Slow Brain Aging 381
1 Introduction 382
2 Antioxidants and Healthy Brain Aging 382
3 Behavioral Enrichment and Healthy Brain Aging 384
4 Antioxidants and Behavioral Enrichment in the Canine Model of Human Aging 385
4.1 Neurobiological and Cognitive Features of the Aged Dog 385
4.2 Cognitive Benefits of Antioxidants and Behavioral Enrichment in Aged Dogs 386
4.3 Neurobiological Changes in Response to Antioxidants and Behavioral Enrichment 387
5 Summary and Conclusions 388
References 388
Role of Nitric Oxide in Neurodegeneration and Vulnerabilityof Neuronal Cells to Nitric Oxide Metabolites and ReactiveOxygen Species 398
1 Introduction 399
1.1 Neuronal Death and Survival Under Oxidative Stress in AD and PD 399
1.2 Superoxide and NO in Senescence and Aging 400
1.3 Role of Reactive Oxygen Species and Reactive Nitrogen Species in Oxidative and Nitrosative Stress and in Aging 400
1.4 Role of NO in Aging, AD, Obesity, and Heart Disease 400
1.5 Role of NO and Cellular Stress Response in Brain Aging and Neurodegenerative Disorders 401
1.6 Interplay Between Superoxide and NO in Aging and Diseases via Many Physiologic Functions 401
2 NO and Its Physiologic Role 401
2.1 Aß, NO, and Synaptic Plasticity 402
2.2 Aß Fragment Impairs Memory and IncreasesNO in the Temporal Cortex of Rats 403
3 The Vulnerability of Different Cell Types to ROS and RNS Insults 403
4 Use of SNP to Study the Susceptibility of Different Cell Types Toward Free Radicals 404
5 Different Cell Types Generate NOx Differently When Treated with SNP 404
5.1 Increased Levels of NOx Release in SNP-Treated Astrocytic and Epithelial Cell Lines 404
5.2 Reduced Levels of NOx Release in SNP-Treated Neuronal Cell Lines 405
6 SNP-Induced Cell Death 406
7 NOS in Different Cell Types 406
7.1 Lack of NOS Activity in U-138, C6, and HeLa Cells 406
7.2 Presence of NOS Activity in N1E-115 Cells 406
7.3 Inhibition of NOS Activity by SNP 407
8 Effects of Different Agents on NOx Production and LDH Release in Astrocytic Cells 407
8.1 High Dose of IL-1ß Decreased Nitrite Production in C6 CellsWhen Stimulated with SNP 407
8.2 Inhibition of NOx Release with Carboxyl-PTIO Treatment 407
8.3 Inhibition of NOx Release with SOD-1 Treatment 408
8.4 L-NAME Treatment Did Not Change the Release of NOx Release 408
9 Pathway of NOx Production in Various Cell Types 408
10 Mechanism of NOx Production from SNP 409
11 Levels of NOx and Cellular Viability 410
12 Protective Cellular Mechanism to Reduce the SNP-Induced Toxicity 410
13 Relationship Between the Enzymatic and Nonenzymatic Pathways of NO Release 411
14 Cellular Participation for the Generation of NOx 411
15 Role of Melatonin in the Inhibition of NOx Release 411
16 Relationship Between NO Metabolites, Antioxidants, and AD 412
References 412
Free RadicalMediated Damage to Brain in Alzheimers Disease: Role of Acrolein and Preclinical Promise of Antioxidant Polyphenols 415
1 Introduction 415
1.1 Free Radical'Mediated Damage to Brain During Aging and in Alzheimer's Disease 415
2 Markers of Free RadicalMediated Damage in Transgenic Mouse Models 419
3 Acrolein as a Potential Inducer of Oxidative Stress and Its Role in AD 421
4 Dietary Antioxidants and Risk of AD: Mechanisms of Action 424
5 Conclusions 428
References 429
An Epigenetic Model for Susceptibility to Oxidative DNAINTbreak Damage in the Aging Brain and Alzheimer's Disease
1 Introduction 436
2 Epigenetics and AD 437
3 Oxidative Stress and AD 438
4 Exposure to Lead and the Developmental Basis of AD 439
5 Epigenetics, the Environment, and Load 440
6 DNA Methylation and DNA Oxidation 442
7 Summary and Conclusions 444
References 445
Index 451

Produkt-Details

• Erscheint lt. Verlag: 2.9.2010
• Reihe/Serie: Oxidative Stress in Applied Basic Research and Clinical Practice
• Reihe/Serie: Oxidative Stress in Applied Basic Research and Clinical Practice
• Zusatzinfo: XVI, 472 p.
• Verlagsort: Totowa
• Sprache: englisch
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Geriatrie
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Biochemie / Molekularbiologie
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Physiologie
• Themenwelt: Naturwissenschaften ► Biologie ► Mikrobiologie / Immunologie
• Themenwelt: Naturwissenschaften ► Biologie ► Zellbiologie
• Themenwelt: Technik
• Schlagworte: Age • Aging, Oxidative Stress, Neurology • Alzheimer • Cells • Development • Influence • Regulation
• ISBN-10: 1-60761-602-5 / 1607616025
• ISBN-13: 978-1-60761-602-3 / 9781607616023