Biology of Human Longevity (eBook)

Front Cover 1
The Biology of Human Longevity 4
Copyright Page 5
Contents 6
Preface 12
Acknowledgments 14
Chapter 1: Inflammation and Oxidation in Aging and Chronic Diseases 15
Part I 16
1.1. Overview 16
1.2. Experimental Models for Aging 24
1.2.1. Mortality Rate Accelerations 24
1.2.2. Mammals 26
1.2.3. Cultured Cell Models and Replicative Senescence 45
1.2.4. Invertebrate Models 46
1.2.5. Yeast 48
1.2.6. The Biochemistry of Aging 49
1.2.7. Biomarkers of Aging and Mortality Risk Markers 56
1.2.8. Evolutionary Theories of Aging 58
1.3. Outline of Inflammation 63
1.3.1. Innate Defense Mechanisms 64
1.3.2. Genetic Variations of Inflammatory Responses 68
1.3.3. Inflammation and Energy 70
1.3.4. Amyloids and Inflammation 73
1.4. Bystander Damage and Dependent Variables in Senescence 74
1.4.1. Free Radical Bystander Damage (Type 1) 75
1.4.2. Glyco-oxidation (Type 2) 77
1.4.3. Chronic Proliferation (Type 3) 77
1.4.4. Mechanical Bystander Effects (Type 4) 78
Part II 79
1.5. Arterial Aging and Atherosclerosis 79
1.5.1. Overview and Ontogeny 80
1.5.2. Hazards of Hypertension 88
1.5.3. Mechanisms 89
1.5.3.1. Inflammation 89
1.5.3.2. Hemodynamics 93
1.5.3.3. Aging 95
1.5.3.4. Endothelial Progenitor Cells 98
1.5.4. Blood Risk Factors for Vascular Disease and Overlap with Acute Phase Responses 98
1.6. Alzheimer Disease and Vascular-related Dementias 100
1.6.1. Neuropathology of Alzheimer Disease 101
1.6.2. Inflammation in Alzheimer Disease 105
1.6.3. Prodromal Stages of Alzheimer Disease 108
1.6.4. Overlap of Alzheimer and Cerebrovascular Changes 109
1.6.5. Insulin and IGF-1 in Vascular Disease and Alzheimer Disease 113
1.6.6. Blood Inflammatory Proteins: Markers for Disease or Aging, or Both? 115
1.7. Inflammation in Obesity 117
1.8. Processes of Normal Aging in the Absence of Specific Diseases 120
1.8.1. Brain 121
1.8.2. Generalized Inflammatory Changes in Normal Tissue Aging 121
1.9. Summary 126
Chapter 2 :Infections, Inflammogens, and Drugs 127
2.1. Introduction 128
2.2. Vascular Disease 128
2.2.1. Historical Associations of Infections and Vascular Mortality 128
2.2.2. Modern Serologic Associations 129
2.3. Infections from the Central Tube: Metchnikoff Revisited 135
2.3.1. Humans: Leakage from Periodontal Disease and Possibly the Lower Intestine 135
2.3.2. Worms and Flies as Models for Human Intestinal Microbial Intrusion 139
2.4. Aerosols and Dietary Inflammogens 140
2.4.1. Aerosols 141
2.4.2. Food 143
2.5. Infections, Inflammation, and Life Span 145
2.5.1. Historical Human Populations 145
2.5.2. Longer Rodent Life Spans with Improved Husbandry 150
2.6. Are Infections a Cause of Obesity? 156
2.7. Inflammation, Dementia, and Cognitive Decline 157
2.7.1. Alzheimer Disease 157
2.7.2. HIV, Dementia, and Amyloid 159
2.7.3. Peripheral Amyloids 161
2.7.4. Inflammation and Cognitive Decline During ‘Usual’ Aging 161
2.8. Immunosenescence and Stem Cells 164
2.8.1. Immunosenescence and Cumulative Exposure 164
2.8.2. Immunosenescence and Telomere Loss 166
2.8.3. Inflammation and Stem Cells 167
2.9. Cancer, Infection, and Inflammation 168
2.9.1. Helicobacter Pylori and Hepatitis B Virus 168
2.9.2. Smoking and Lung Cancer 170
2.10. Pharmacopleiotropies in Vascular Disease, Dementia, and Cancer 172
2.10.1. Anti-inflammatory and Anti-coagulant Drugs 172
2.10.2. Aspirin and Other NSAIDs 175
2.10.3. Statins 176
2.10.3.1. Vascular Disease 176
2.10.3.2. Dementia 178
2.10.4. Sex Steroid Replacement (Hormone Therapy) 179
2.10.5. Plant-derived Micronutrients and Neutriceuticals 183
2.11. Summary 186
Chapter 3: Energy Balance, Inflammation, and Aging 189
3.1. Introduction 190
3.2. Diet Restriction and Aging 191
3.2.1. Overview of Animal Models 191
3.2.2. Diet Restriction and Disease in Rodent Models 198
3.2.3. Diet Restriction, Starvation, Vascular Disease, and Longevity in Humans 200
3.2.4. Diet Restriction, Infections and Inflammation 206
3.2.5. Somatic Repair and Regeneration 213
3.3. Energy Sensing in Diet Restriction and Satiety 214
3.3.1. Physiology 215
3.3.2. Biochemistry 216
3.3.3. Relevance to Arterial Disease and Cancer 224
3.4. Exercise, Cardiovascular Health, and Longevity 225
3.4.1. Humans 226
3.4.2. Rodent Models 229
3.4.3. Mechanisms in Exercise and Longevity 230
3.5. Diet, Exercise, and Neurodegeneration 233
3.5.1. Alzheimer Disease 233
3.5.2. Synaptic Atrophy in the Absence of Neurodegeneration 235
3.6. Laboratory Rodents as Models for the ‘Couch Potato’ 239
3.7. Energy Balance in the Life History 242
3.8. Summary 245
Chapter 4: Nutrition and Infection in the Developmental Influences on Aging 247
4.1. Introduction 248
4.2. Synopsis of the Fetal Origins Theory 250
4.3. The Barker Studies of Infections and Vascular Disease 255
4.4. Size, Health, and Longevity 259
4.4.1. Adult Height, Vascular Disease, and Longevity 260
4.4.2. Size at Birth and Adult Height 263
4.4.3. Criteria for Growth Retardation 266
4.4.4. Maternal Metabolism and Fetal Growth 268
4.4.5. Birth Size and Adult Vascular and Metabolic Disease 272
4.4.6. Twins: Small Size at Birth and Catch-up Growth, but Normal Longevity 276
4.5. Infection and Undernutrition on Birth Weight and Later Disease 276
4.5.1. The Tangle 277
4.5.2. Maternal Infections and Nutrition 277
4.5.3. Smoking and Aerosols 281
4.6. Infection and Nutrition in Postnatal Development and Later Disease 281
4.6.1. Diarrheas in Growth Retardation 281
4.6.2. Seasonal Effects 282
4.6.3. Serum Immune Response Markers of Chronic Infection in Health-Poor Children 284
4.6.4. Infections During Development 286
4.6.5. The Cost of Infections to Postnatal Growth: Evidence from Migration and Antibiotics 287
4.6.6. Unknowns 289
4.7. Famine 290
4.7.1. World War II (WWII) 290
4.7.2. 19th Century Famines 300
4.8. Maternal Physiology, Fetal Growth, and Later Chronic Disease 303
4.9. Growth in Adaptive Responses to the Environment 309
4.10. Genomics of Fetal Growth Regulation 312
4.10.1. Inherited Genetic Variations 313
4.10.2. Gene Imprinting: Inherited but Epigenetic Influences on Development 313
4.11. Summary 316
Chapter 5: Genetics 319
5.1. Introduction 320
5.2. Sources of Individual Variations in Aging and Life Span 320
5.3. Sex Differences in Longevity 324
5.4. Metabolism and Host-Defense in Worm and Fly 329
5.4.1. Metabolic Gene Signaling 329
5.4.2. Immunity and Metabolism 332
5.5. The Worm 337
5.5.1. Overview 337
5.5.2. Slower Eating Increases Life Span 339
5.5.3. Metabolism and Host Defense 339
5.6. Fly 343
5.6.1. Overview 343
5.6.2. Metabolism and Diet Restriction 344
5.6.3. Heart 347
5.6.4. Infections, Host Defense, and Stress Resistance 349
5.6.5. Natural Variations in Longevity Pathways 351
5.7. Mammals 352
5.7.1. Growth and Metabolism 352
5.7.1.1. Rodent Mutants with Altered Insulin Signaling and Fat Metabolism 357
5.7.1.2. Human Hereditary Variations in Metabolic Genes 365
5.7.1.3. Size and Longevity 368
5.7.1.4. The Insulin-Sensitivity Paradox 369
5.7.2. Inflammation 369
5.7.3. Lipoproteins and Cholesterol Metabolism 371
5.7.4. ApoE4 Interactions with Diet, Cognition, and Vascular Aging 377
5.7.5. ApoE Alleles, Infection, and Reproduction 382
5.8. Summary 384
Chapter 6: The Human Life Span: Present, Past, and Future 387
6.1. Introduction 387
6.2. From Great Ape to Human 390
6.2.1. Human Life History Evolution 390
6.2.2. Chimpanzee Aging 397
6.2.3. The Evolution of Meat-Eating 399
6.2.4. Meat Adaptive Genes 405
6.2.5. The Increase in Life Expectancy 416
6.3. Four Major Shifts in Human Life History from Genetic and Cultural Evolution 418
6.4. The Instability of Life Spans 420
6.4.1. Infections 420
6.4.2. Air Quality 423
6.4.3. Obesity and Diabetes 424
6.4.4. Prospects 426
6.5. Summary of Chapters 1–6: Mechanisms in Aging and Life History Evolution 427
References 431
Name Index 615
Subject Index 628