Hormesis : a revolution in biology, toxicology, and medicine

Hormesis is defined as any circumstance in which exposure of a cell or organism to a low dose of a substance or condition results in an adaptive stimulatory/beneficial outcome, while exposure to a high dose results in an inhibitory / detrimental outcome. When plotted on a graph the shape of the dose response curve is biphasic, the hallmark of hormesis. This groundbreaking book "Hormesis: A Revolution in Biology, Toxicology and Medicine" describes why and how hormesis is a fundamental feature of all living systems and is based on the evolutionary principle of selection for genetic traits that confer the ability to respond adaptively to adverse environmental conditions. Using numerous specific examples the authors explain why knowledge of hormesis is important for our health, our environment, and the future of our planet. Several chapters of the book describe emerging research findings that elucidate the molecular and cellular underpinnings of the biphasic dose response/hormesis. The implications of the tapping of cellular systems that underlie hormesis for the discovery and optimization of new drugs and dietary formulations are described. From environmental protection policy to medical practice, it is critical that leaders recognize and understand hormesis, and incorporate it into their decision making process. The authors propose that the prevention of major diseases, including diabetes, obesity and cardiovascular disease can be achieved using hormetic approaches. Scientists, physicians, environmental gurus and anyone interested in the science underlying biology and medicine will benefit from reading this book. Features * Groundbreaking coverage of an oft experienced, but poorly understood phenomenon that affects all forms of life on earth. * Explains why the principle of hormesis is important to our health, our environment, and the future of our planet. * Provides specific examples of biphasic dose responses and their importance for the fields of biology, medicine and environmental safety. * Discusses how knowledge of hormesis is being applied to research aimed understanding the organization and function of biological systems. * Illustrates how disorders such as diabetes, obesity and cardiovascular disease result from the lack of exposure to beneficial environmental stresses. * Considers the implications of the cellular systems that underlie hormesis for the discovery and optimization of new drugs and dietary formulations. Cover 1 Frontmatter 2 Preface 5 Contents 8 About the Editors 9 Contributors 10 Hormesis: What It Is and Why It Matters 12 Hormesis Is a Fundamental Feature of Biological Systems 13 Hormesis Is a Manifestation of a Fundamental Feature of Evolution 15 Cellular and Molecular Mediators of Hormetic Responses 17 Hormesis in Medicine: Dose and Frequency of Treatment Are Both Important 18 Are Beneficial Chemicals in Fruits and Vegetables Toxins Acting at Low Doses? 20 Hormesis Is Not Homeopathy 21 Implications of Hormesis for the Practices of Environmental Protection and Medicine 21 Hormesis: Once Marginalized, Evidence Now Supports Hormesis as the Most Fundamental Dose Response 25 Introduction 26 Historical Antipathies, Rather Than Science, Determined Which DoseResponse Model Would Dominate Biology 27 The Hormetic Dose-Response Relationship 30 The Hormesis Database 32 The Frequency of Hormesis in Toxicology and Pharmacology 40 Implications of Hormesis 41 Impact on Biological Concepts 42 Hormesis Measures Performance 42 Hormesis Provides Quantitative Estimates of Biological Plasticity 42 Adaptive Response/Preconditioning: Manifestations of Hormesis 43 Hormesis as an Expression of Allometry 43 Toxicological/Pharmacological Implications 44 Factors Affecting the Recognition of Hormetic Dose-Response Relationships 44 Use of Multiple Terms 44 Modest Stimulation and Historically Weak Study Designs 44 Control Group: High Variation 44 Low Background Disease Incidence 45 Lack of Temporal Component 45 Summary 45 Chemical Potency and Hormesis 45 Hormesis: A Novel Concept of Synergy/Potentiation 46 Interindividual Variation and Hormesis 47 Epidemiology and Hormesis 48 Hormesis and Medicine 48 Low-Dose Stimulation of Tumor Cells 48 Low-Dose Stimulation of Microbes by Antibiotics 49 Anxiolytic Drugs 49 Antiseizure Drugs 50 Memory-Enhancing Drugs 50 Stroke Medications 51 Osteoporosis 51 Hair Growth 52 Pulmonary Hypertension 52 Fibrotic Diseases (e.g., Dupuytren's Contracture) 52 Avoidance of Undesirable Side Effects 52 Environmental Risk Assessment 53 Discussion 60 The Fundamental Role of Hormesis in Evolution 67 Introduction 67 The Biphasic Dose Response and Evolution 69 Cellular and Molecular Hormetic Mechanisms 72 Hormesis and Evolutionary Strategies: Diversification and Specialization 73 Conclusions and Future Directions 76 Transcriptional Mediators of Cellular Hormesis 79 Introduction 79 Nature of Transcriptional Regulation 80 Hormetic Signaling Pathways 81 Nuclear Factor--Erythroid 2p45 (NF-E2)--Related Factor (Nrf2)/Antioxidant Response Element (ARE) Signaling Pathway 82 Nrf2, Keap1, and Regulation of the ARE Pathway 82 Hormetic Inducers of the Nrf2/ARE Pathway 84 Forkhead Box O (FOXO) Transcription Factors 86 FOXO, Oxidative Stress, and Longevity 89 The Nuclear Factor-B Pathway 90 NF-B as a Hormetic Transducer of Exercise 91 Heat-Shock Factor Pathway 92 Conclusions 96 The Devil Is in the Dose: Complexity of Receptor Systemsand Responses 104 Introduction 104 Classic and Modern Dynamic GPCR Models 105 Receptor System Complexities and Responses 107 Multiple G Protein Coupling 107 Allosteric Receptor Modulation 108 Receptor Desensitization 110 Receptor Dimerization 111 GPCRs and Receptorsome Structures 112 Conclusions 113 Exercise-Induced Hormesis 118 Introduction 118 Effects of Exercise on the Musculoskeletal System 119 Dose-Response Characteristics of Exercise Effects on Muscle 119 Duration-Dependent Effects of Exercise on Bone 120 Effects of Exercise on the Digestive System 120 Dose-Dependent Effects of Exercise on the Stomach 120 Hormetic Effects of Exercise in the Large and Small Intestine 120 Dose-Response Characteristics of Exercise Effects on the Liver 120 Duration-Dependent Effects of Exercise on the Pancreas 121 Effects of Exercise on the Reproductive System 121 Dose-Response Characteristics of Exercise Effects on Ovarian Function 121 Duration-Dependent Effects of Exercise on the Testis 122 Effects of Exercise on the Cardiorespiratory System 122 Duration-Dependent Effects of Exercise on the Heart 122 Dose-Dependent Effects of Exercise on the Lungs 123 Effects of Exercise on the Immune System 123 Dose-Response Characteristics of Exercise Effects on the Thymus 123 Hormetic Effects of Exercise on the Spleen 123 Exercise Effects on Circulating Cytokines Conform to the Theory of Hormesis 124 Effects of Exercise on the Brain 124 Duration-Dependent Effects of Exercise on Adult Neurogenesis 124 Dose-Response Characteristics of Exercise Effects on Dendritic Spines 125 Duration-Dependent Effects on Angiogenesis 126 Duration-Dependent Effects of Running on Neurotrophic Factor Expression 126 Conclusion 127 Dietary Energy Intake, Hormesis, and Health 132 Introduction 132 CR as a Hormetic Effector 133 CR and Cellular Stress Factors 134 CR Effects Upon Cytokine Levels 135 CR and Alterations in Neurotrophic Factors 136 CR Effects Upon Glycemic Control 136 CR and Satiety/Adipose-Generated Hormones 137 CR and Ketone Body Synthesis 138 CR and Sirtuin Activity 138 CR Modulation of PPARs and Cofactors 139 CR and Transcriptional Regulation 140 Conclusions 141 Couch Potato: The Antithesis of Hormesis 147 The Couch Potato Caricature 148 Advances in Technology Reveal the Dangers of a Sedentary Lifestyle 149 Cellular and Molecular Mechanisms of Exercise Hormesis 149 Calories In, Disease Out 152 In One Ear and Out the Other 153 Implications of Hormesis for the Future of the Couch Potato 155 Hormesis and Aging 160 Introduction 160 Recapitulating the Biological Basis of Aging 161 Thermal Hormesis in Aging 164 Thermal Hormesis in Organisms 164 Thermal Hormesis in Human Cells Undergoing Aging in Vitro 165 Hypergravity Hormesis in Aging 168 Radiation Hormesis in Aging 168 Radiation Hormesis in Insects 168 Radiation Hormesis in Rodents and Other Animals 169 Radiation Hormesis in Humans 169 Calorie Restriction and Hormesis 170 Exercise Hormesis 171 Nutritional Hormesis and Hormetins 172 Other Stresses 173 Hormesis Potential, Challenges, and Unresolved Issues in Aging 174 The Hormetic Pharmacy: The Future of Natural Productsand Man-Made Drugs in Disease Prevention and Treatment 183 Introducing the Pharmacist to Hormesis 183 Why the Pharmaceutical Industry Is Missing the Hormesis Revolution 184 Hormesis and Biological Plasticity 185 Dietary Factors 185 Drugs 187 Implications of the Quantitative Features of the Hormetic Dose Response for the Pharmaceutical and Nutraceutical Worlds 188 Biological Model Selection 188 Drug-Testing Strategies 189 Drug Potency 190 Drug--Drug Interactions 190 Clinical Trials and Hormesis 191 Potentially Harmful Hormetic Responses 191 Hormesis in the Pharmaceutical Industry 194 Anxiolytic Drugs 194 Antiseizure Drugs 195 Male Sexual Dysfunction 195 Diabetes 196 Memory/Cognition 196 Osteoporosis 197 Hormesis and Neutraceuticals 197 Hormetic Mimetics 199 Discussion 200 Index 205 Front Matter....Pages i-xiv Hormesis: What it is and Why it Matters....Pages 1-13 Hormesis: Once Marginalized, Evidence Now Supports Hormesis as the Most Fundamental Dose Response....Pages 15-56 The Fundamental Role of Hormesis in Evolution....Pages 57-68 Transcriptional Mediators of Cellular Hormesis....Pages 69-93 The Devil is in the Dose: Complexity of Receptor Systems and Responses....Pages 95-108 Exercise-Induced Hormesis....Pages 109-122 Dietary Energy Intake, Hormesis, and Health....Pages 123-137 Couch Potato: The Antithesis of Hormesis....Pages 139-151 Hormesis and Aging....Pages 153-175 The Hormetic Pharmacy: The Future of Natural Products and Man-Made Drugs in Disease Prevention and Treatment....Pages 177-198 Back Matter....Pages 199-213 Hormesis is a poorly understood phenomenon affecting all forms of life on earth. This groundbreaking book summarizes and analyzes the various positives of hormesis in an attempt to reveal hormesis as a fundamental principle of biomedical sciences as a whole. Mark P. Mattson, Edward J. Calabrese, Editors. Includes Bibliographical References And Index.