The Neuroendocrine Immune Network in Ageing
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Table of contents
- Coveriii
- List of Contributorsv
- Contentsxi
- I. Introduction1
- Evolutionary Aspects for the Neuroendocrine Immune Network in Ageing3
- Abstract3
- Adeing of One Supersystem Affects Ageing of Another Supersystem3
- Advantageous Mechanisms for Ageing and Longevity are not Evolutionarily Conserved4
- Review for this Book5
- References5
- II. Ageing of the Immune System7
- lmmunosenescence9
- Abstract9
- Introduction9
- The Effect of Ageing on Thymopoiesis10
- Senescence of Naive T Cells11
- Signal Transduction in Aged T Lymphocytes12
- Age-Associated Alterations of Alpha/Beta T Lymphocytes12
- Age-Associated Alterations in the T Cell Repertoire14
- "Replicative Senescence" of in Vivo Expanded T Cells14
- Age-Associated Alterations of Gamma/Delta T Lymphocytes and NKT Cells15
- Funtional Changes Resulting from the above Age-Associated Alternators and the Effect of Pyschologica15
- Conclusion: How Important is Imminosenescence Clinically?16
- Acknowledgements16
- References17
- Zinc-Binding Proteins (Metallothionein and Alpha-2 Macroglobulin) as Potential Biological Markers of23
- Abstract23
- Introduction23
- The Biology of Zinc24
- The Biology of Zinc-Binding Proteins26
- Metallothioneins26
- Alpha-2 Macroglobulin27
- Zinc, Immune System and Ageing28
- Metallothionein, The Immune System and Ageing30
- Alpha-2 Macroglobulin, the Immune System and Ageing31
- Zinc Supplementation33
- Conclusions and Predictions for the Future34
- Acknowledgments35
- References35
- Neutrophil Ageing and Immunosenescence41
- Abstract41
- The Ageing Process41
- Ageing and Infectious Disease42
- Neutrophils and Neutrophil Ageing43
- Ageing and Neutrophil Function45
- Neutrophil Production45
- Neutrophil Extravasation and Chemotaxis46
- Neutrophil Phagocytosis of Pathogens46
- Neutrophil Intracellular Bactericidal Processes47
- Neutrophil Priming47
- Mechanisms Underlying Reduced Neutrophil Phagocytosis48
- Ageing and Adrenal Steriod Production49
- DHEA Supplementation and Immune Function50
- Trauma Responses in the Elderly51
- Concluding Remarks52
- Acknowledgements52
- References52
- Apoptosis and Ageing57
- Abstract57
- Introduction57
- T Cell Apoptosis and Ageing58
- Death Receptor Pathway59
- TNF-Alpha, Apoptosis and Ageing59
- Signalling through TNF-RI59
- Signalling through TNF-RII60
- The Fas/FasL Receptors and Ageing61
- Receptors and Lipid Rafts62
- The Mitochondrial Pathway63
- Role of Free Radicals in Inducing Apoptosis63
- Apoptosis Polymorphonuclear Neutrophils (PMN) and Ageing64
- Apoptosis of PMNs64
- GM-CSF and PMN Apoptosis65
- Free Radical Production of PMNs66
- Conclusions and Future Perspectives66
- Acknowledgements67
- References67
- MHC-Unrestricted Cytotoxicity in Ageing73
- Abstract73
- Premises73
- Macrophages74
- Polymorphonuclear Leukocytes75
- Natural Killer Cells76
- GammaSigma T Cells79
- MHC-Unrestricted Immunity: Impact on the Senescence of Adaptive Immune Responses80
- References81
- Major Histocompatibility Complex Polymorphisms and Ageing91
- Abstract91
- Introduction: The Major Histocompatibility Complex91
- HLA IA & II Class Alleles in Ageing95
- HLA IB Alleles in Ageing95
- HLA III Class Alleles in Ageing96
- Concluding Remarks98
- Acknowledgements98
- References98
- III. Ageing of the Endocrine System103
- Neuroplasticity in the Human Hypothalamus During Ageing105
- Abstract105
- Introduction106
- Preoptic or Chiasmatic Region106
- Suprachiasmatic Nucleus106
- Sexually Dimorphic Nucleus (Intermediate Nucleus, INAH-1)109
- Supraoptic and Paraventricular Nuclei110
- Nucleus Basalis of Meynert111
- Tuberal Region113
- Ventromedial and Dorsomedial Nuclei113
- Arcuate (Infundibular) Nucleus114
- Lateral Tuberal Nucleus115
- Concluding Remarks115
- Acknowledgements116
- References116
- The Role of Growth Hormone Signaling in the Control of Ageing123
- Abstract123
- Introduction123
- Studies of Longevity Genes Link IGF Signaling to the Control of Ageing124
- Search for Mechanisms that Link Reduced GH and IGF-1 Signaling with Delayed Ageing125
- Activity of the Somatotropic Axis, Growth and Adult Body Size126
- Reduced Insulin Levels and Increased Sensitivity to Insulin127
- Body Temperature, Metabolic Rate, and Oxidative Stress127
- Conflicting Findings128
- GH Levels Decline with Age129
- Potential Use of GH in Anti-Ageing Medicine129
- Possible Protective Role of Age-Related Decline in Somatotropic Activity130
- Relationship of GH Actions during Different Stages of Life History to the Regulation of Ageing and L131
- Implications for Possible Anti-Ageing Strategies132
- Acknowledgements132
- References132
- Ageing and the Adrenal Cortex139
- Abstract139
- Introduction139
- Andrenal Androgen Secretion and Ageing140
- Regulation of Androgen Production141
- Extra-Adrenal Regulation of Adrenal Androgens141
- Intra-Adrenal Regulation of Adrenal Androgens142
- Adrenarche/Andropause143
- Regulation of Adrenopause143
- Functional Significance145
- Conclusion146
- References146
- Hormonal Changes in Ageing Men153
- Abstract153
- Introduction153
- Gender Related Differences of the Endocrine System during Ageing154
- Hypogonadism in Elderly Men154
- Longitudinal Endocrine Changes in Ageing Men156
- Decline in Pulsatile Hormone Secretion with Age156
- Impact of Health Status on Serum Androgen Levels157
- Androgen Supplementation in Ageing Males158
- General Considerations158
- Indications for Androgen Supplementation158
- Depression and Androgen Supplementation159
- Body Composition and Androgen Supplementation159
- Bone Metabolism and Androgen Supplementation159
- Side Effects of Androgen Supplementation159
- Senieur Protocol - An Optimised Study Population to Investigate Male Ageing160
- Conclusions160
- References161
- Ageing and the Endocrine Circadian System165
- Abstract165
- Introduction165
- Adrenal Hormones Circadian Rhythm166
- Melatonin Circadian Rhythm168
- Hypothalamic-Pituitary-Thyroid (HPT) Axis170
- Clinical Considerations170
- Thyrotropin Releasing Hormone (TRH)171
- Thyroid Stimulating Hormone (TSH)171
- Thyroid Hormone172
- Seasonal Variations and/or Circannual Rhythms of the HPT Axis173
- Prolactin (PRL)174
- Hyperprolactinemia175
- Prolactin and the Immune System175
- Catecholamines176
- Central and Tissue Catecholamines176
- Conclusion179
- References180
- Melatonin Rhythms, Melatonin Supplementation and Sleep in Old Age195
- Abstract195
- Introduction195
- The Circadian Timing System196
- Structure of the Suprachiasmatic Nucleus196
- Input to the Suprachiasmatic Nucleus196
- Output of the Suprachiasmatic Nucleus Innervating the Pineal Gland196
- The Pineal Gland and its Main Hormone Melatonin198
- Melatonin Function and Sites of Action199
- Age-Related Changes in the Circadian Timing System199
- Age-Related Changes in the Suprachiasmatic Nucleus199
- Age-Related Changes in Melatonin Levels, Amplitude and Rhythmicity200
- Functional Implications of Weak or Distributed Circadian Rhythms201
- Interactions with Drugs Frequently Used by Elderly201
- Melatonin Supplementation and Consequences for the Circadian Timing System202
- Pharmacokinetics202
- Clinical Studies on the Effects of Exogenous Melatonin on Sleep in the Elderly203
- Adverse Effects and Dosage206
- Conclusive Remarks206
- Acknowledgements207
- References207
- IV. Ageing of the Nervous System213
- Age-Related Changes of the Human Autonomic Nervous System215
- Abstract215
- Influence of Age on Autonomic Nervous System (ANS) Function: Methodological Aspects and Limitations215
- Influence of Age on the Heart and the Blood Vesels216
- Effects of Ageing on Resting Heart Rate217
- Effects of Ageing on Cardiovagal Heart Rate Tests218
- Short-Term Resting Heart Rate Variability (HRV)218
- HRV During Deep Respiration222
- Heart Rate Response to Standing223
- Valsalva-Test225
- Effects of Ageing on Baroreflexes and Blood Pressure226
- References227
- Age-Related Alterations in Autonomic Nervous Innervation233
- Abstract233
- Introduction233
- Bone Marrow234
- Age-Related Changes in Bone Marrow234
- Sympathetic Innervation of Bone Marrow234
- Age-Related Changes in Sympathetic Innervation of Bone Marrow234
- Functional Significance of NA Innervation of Bone Marrow234
- Thymus235
- Structure and Function of the Thymus235
- Age-Related Changes in the Thymus236
- Sympathetic Innervation of the Thymus236
- Sympathetic Innervation in the Ageing Thymus237
- Functional Studies and Significance237
- Spleen239
- Structure and Function of the Spleen239
- Sympathetic Innervation of the Spleen240
- Sympathetic Innervation in the Ageing Spleen240
- Can Age-Related Changes in NA Innervation be Reversed?242
- Age-Related Changes in the Spleen and Immune Function243
- Functional Studies and Significance243
- Summary and Closing Remarks246
- References247
- Ageing and the Neumendocrine System of the Gut257
- Abstract257
- Introduction257
- The Neuroendocrine System of the Gut258
- Age-Related Changes in the Gut Neuroendocrine System260
- Endocrine Cells260
- The Enteric Nervous System262
- Age-Related Changes and Gastrointestinal Disorders in the Elderly264
- Clinical Implications266
- Conclusion267
- Acknowledgement268
- References268
- Modulating Effects of Nutrition on Brain Ageing273
- Abstract273
- Introduction274
- Nutritional Interventions and Methods274
- Dietary Restriction274
- Animals and Diet274
- Quantitative Analysis of Synoptic Dynamic Morphology274
- Vitamin E Deficiency275
- Animals and Diet275
- Quantitative Analysis of Synaptic Dynamic Morphology276
- Quantitative Cytochemistry of Succinic Dehydrogenase (SDH) Activity in Purkinje Cell Mitochondria276
- Intracellular Ionic Content277
- Chronic Ethanol Administration277
- Animals and Diet277
- Quantitative Analysis of Synaptic Dynamic Morphology277
- lntracellular Ionic Content278
- Results279
- Dietary Restriction279
- Vitamin E Deficiency280
- Chronic Ethanol Administration281
- Discussion282
- Dietary Restriction282
- Synaptic Dynamic Morphology282
- Vitamin E Deficiency284
- Synaptic Dynamic Morphology284
- SDH Activity in Purkinje Cell Mitochondria284
- Intracellular Ionic Content285
- Chronic Ethanol Administration285
- Synaptic Dynamic Morphology285
- Intracellular Ionic Content286
- Conclusions286
- References287
- Ageing-Related Role of Nitric Oxide in the Brain291
- Abstract291
- Introduction291
- Nitric Oxide292
- No Synthase292
- Homeostasis of No System293
- Role of NO in the Brain293
- Ageing-Related Changes in the No Production295
- Endothelial NOS in the Brain during Ageing296
- Neuronal NO Synthase in the Brain during Ageing296
- Inducible NO Synthase in the Brain during Ageing297
- Concluding Remark298
- References298
- V. Links between One Global System and another Global System during the Ageing Process301
- Introduction: Links Between One Global System and Another Global System During the Ageing Process303
- Abstract303
- Ageing of One Part of Global System Involves another part of another Global System303
- DHEA and IL-6303
- Zinc, Hormones and Thymic Function304
- Glucocorticoids and Brain Function304
- Hormone Loss and Osteoporosis304
- Conclusions304
- References305
- Plasticity of Neuroendocrine-thymus Interactions During Ontogeny and Ageing: Role of Zinc307
- Abstract307
- Introduction307
- Neuroedocrine-Thymus Interactions: The Strategic Circuit in Ontogeny311
- Intrathymic T-cell Differentiation and Maturation311
- Paracrine Cycle of Cytokines on Thymic Microenviromental Cells312
- Cytokines as Immunotransmitters towards the HP Axis313
- Neuroendocrine Influence on Thymic Functions and Vice Versa315
- Neuroendocrine Influence on Thymic Functions315
- Thymic Influence on the Neuroendocine Sytem316
- The Role of Zinc316
- Neuroendocrine-Thymus Interactions during Ageing318
- Thymic Rejuvenation by Nutritional Approach: The Example of Zinc319
- Thymic Rejuvenation by Neuroendocrine Approacb320
- The Example of Growth Hormone320
- The Example of Melatonin321
- Is there a Unique Meditor for Hormone-Induced Thymic Rejuvenation?322
- Acknowledgments323
- References323
- Adverse Glucocorticoid Actions and their Relevance to Brain Ageing331
- Abstract331
- Introduction331
- GCS and Ageing332
- An Overview of the Adverse CNS Actions of Glucocorticoids332
- Necrotic Neurological Insults and "Endangerment" by Stress and/or Glucocorticoids334
- Mechanisms Mediating the GC Endangerment335
- Disruption of Neuronal Energetics [48]335
- Endangering GC Actions that are Independent of Energetic Effects335
- Disruption of Cellular Defenses335
- Triggering/worsening Apoptosis336
- Glucocorticoid Endangerment and a Seeming Paradox336
- CGS and the Immune System336
- GCs and Immunosenescence337
- GC Effects on CNS vs. Peripheral Inflammation338
- Stress and Ageing339
- Acknowledgements339
- References339
- Neuroendocrine Immune Aspects of Osteoporosis During the Ageing Process347
- Abstract347
- Introduction347
- The Bone Remodeling Process348
- Bone Formation/Resorption Coupling348
- Regulation of Osteoblast Differentiation and Activity348
- Regulation of Osteoclast Differentiation and Activity348
- Ageing of Bone: Alterations in Bone Cell Precursor Pool Sizes and Differentiation349
- Neuro/Endocrine/Immune Circuits in Control of Bone Turnover350
- Peripheral Effects of Neuropeptides on Bone Turnover350
- Calcitonin, CGRP, and VIP350
- NPY and Alpha-Melanocyte Stimulating Hormone (Alpha-MSH)351
- Central Nervous Control of Bone Turnover351
- Leptin, NPY and Ageing352
- Neuroendocrine Regulation of Cytokine Expression: Relevance for Bone Turnover352
- The Hypothalamic/Pituitary/Endocrine Gland Axis in Control of Bone Remodeling: Influence of Ageing353
- References354
- VI. The Ageing Process and Chronic Inflammatory diseases361
- Neuroendocrine Immune Mechanisms of Accelerated Ageing in Patients with Chronic Inflammatory Disease363
- Abstract363
- Systemic Inflammation in Chronic Inflammatory Diseases363
- Changes of the Endocrine System364
- ACTH, Cortisol, and Adrenal Androgens364
- Gonadal Hormones364
- Changes of the Metabolic System365
- Homocysteine and Zinc365
- Lipids and Lipoproteins365
- Advanced Glycosylation Products365
- Changes of the Nervous System366
- Neuronal Innervation366
- Autonomic Nervous Reflexes366
- Brain Functions366
- The Sequence of Events of Accelerated Ageing368
- Are there Therapeutic Consequences?368
- References368
- Thyroid Autoimmunity and Ageing375
- Abstract375
- Introduction375
- The Relevance of Thyroid and Thyroid Autoimmune Disease in the Ageing Process376
- Thyroid Autoimmunity and Ageing: Animal Models376
- Thyroid Autoimmunity and Ageing: the Lesson of Centenarians377
- Relevance of Thyroid Abnormalities in the Ageing Process and in Ageing-Associated Diseases377
- Abnormalities of Thyroid Function377
- Autoimmunity379
- Conclusions379
- References380
- The Clinical Importance of Proinflammatory Cytokines in Elderly Populations383
- Abstract383
- Introduction383
- The Inflammatory Response384
- Chronic Elevations of Circulating Cytokines in Elderly Populations384
- Cytokines, Morbidity and Mortality in the Oldest Old385
- TNF-Alpha is Associated with Dementia and Atherosclerosis in Centenarians385
- TNF-Alpha is a Prognostic Risk Marker in Centenarians387
- TNF-Alpha is a Possible Candidate to be a Marker of the Frailty Syndrome387
- The Clinical Significance of other Inflammatory Medicators in Centenarians387
- The Clinical Significance of Cytokines and the Role of IL-6 in Younger Elderly388
- Triggering Signals of Low-Grade Inflammation in Elderly Populations389
- Is Ageing Associated with a Dysregulated Cytokine Response?390
- Concluding Remarks391
- Acknowledgements392
- References392
- VII. Conclusions397
- Possible New Anti-Ageing Strategies Related to Neuroendocrine- Immune Interactions399
- Abstract399
- Introduction399
- L-Deprenyl400
- Ghrelin and Leptin401
- Carnosine402
- No-Donors402
- Conclusions403
- References404
- Concluding Remarks and Future Directions409
- Abstract409
- Introduction409
- Ageing of the Immune System410
- Immunosenescence410
- Metallothioneins as Potential Biological Markers of Immunosenescence410
- Neutrophil Ageing and Immunosenescence411
- Apoptosis and Ageing411
- MHC-Unrestricted Cytotoxity in Ageing411
- MHC Polymorphism and Ageing412
- Ageing of the Endorine System412
- Neuroplasticity in the Human Hypothalamus during Ageing412
- The Role of Growth Hormone Signaling in the Control of Ageing412
- Ageing and the Adrenal Cortex413
- Hormonal Changes in Ageing Men413
- Ageing of the Neuroendocrine Circadian System414
- Melatonin Rhythms, Melatonin Supplementation and Sleep in Old Age414
- Ageing of the Nervous System415
- Age-Related Changes of the Human Autonomic Nervous System415
- Age-Related Alterations in Autonomic Nervous Innervation415
- Ageing and the Neuroendocrine System of the Gut415
- Nutrition and Brain Ageing416
- Ageing-Related Role of Nitric Oxide in the Brain416
- Links between One Global System and Another Global System during the Ageing Process417
- Plasticity of Neuro-Endocrine-Thymus Interactions during the Ontogeny of Ageing: the Role of Zinc417
- Adverse Glucocorticoid Actions and their Relevance to Brain Ageing417
- Neuroendocrine Immune Aspects of Osteoporosis during the Ageing Process418
- The Ageing Process and Chronic Inflammatory Disease418
- Neuroendocrine Immune Mechanisms of Accelerated Ageing in Patients with Chronic Inflammatory Disease418
- Thyroid Autoimmunity and Ageing418
- The Clinical Importance of Proinflammatory Cytokines in Elderly Populations419
- Conclusions419
- New Anti Ageing Strategies Related to Neuroendocrine Immune Interactions419
- The Future420
- References420
- Index429
The book describes the mechanisms involved in the maintenance of neuroendocrine-immune interactions in ageing. The lack of this maintenance leads to the appearance of age-related diseases (cancer, infections, dementia) and subsequent disability. The capacity of some hormones or nutritional factors in restoring and remodelling the neuroendocrine-immune response during ageing is reported presenting possible new anti-ageing strategies in order to reach healthy ageing and longevity.