Mattson / Calabrese Hormesis

A Revolution in Biology, Toxicology and Medicine
1. Auflage 2009
ISBN: 978-1-60761-495-1
Verlag: Humana Press
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 213 Seiten

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, Ph.D. is Chief of the Laboratory of Neurosciences at the National Institute on Aging in Baltimore, where he leads a multi-faceted research team that applies cutting-edge technologies in research aimed at understanding molecular and cellular mechanisms of brain aging and the pathogenesis of neurodegenerative disorders. He is also a Professor in the Department of Neuroscience at Johns Hopkins University School of Medicine. He has published more than 450 original research articles and numerous review articles, and has edited 10 books in the areas of mechanisms of aging and neurodegenerative disorders. Dr. Mattson has trained more than 60 postdoctoral and predoctoral students who have contributed to his being the most highly cited neuroscientist in the world. Edward J. Calabrese, Ph.D. is a Professor and Program Director of
Environmental Health Science, at the University of Massachusetts in Amherst. His research focuses on environmental toxicology with an emphasis on biological factors including genetic and nutritional factors that enhance susceptibility to pollutant toxicity and the environmental implications of toxicological hormesis. Dr. Calabrese has researched extensively in the area of host factors affecting susceptibility to pollutants, and is the author of more than 300 papers in scholarly journals, as well as 24 books in the field of toxicology and environmental pollution. Dr. Calabrese has received numerous awards including, most recently, the prestigious Marie Curie Prize.

Autoren/Hrsg.

Mattson, Mark P.

Calabrese, Edward J.

Inhaltsverzeichnis

1;Hormesis;1
2;Preface;4
3;Contents;7
4;About the Editors;8
5;Contributors;9
6;Hormesis: What It Is and Why It Matters;11
6.1; Hormesis Is a Fundamental Feature of Biological Systems;12
6.2; Hormesis Is a Manifestation of a Fundamental Feature of Evolution;14
6.3; Cellular and Molecular Mediators of Hormetic Responses;16
6.4; Hormesis in Medicine: Dose and Frequency of Treatment Are Both Important;17
6.5; Are Beneficial Chemicals in Fruits and Vegetables Toxins Acting at Low Doses?;19
6.6; Hormesis Is Not Homeopathy;20
6.7; Implications of Hormesis for the Practices of Environmental Protection and Medicine;20
7;References;21
8;Hormesis: Once Marginalized, Evidence Now Supports Hormesis as the Most Fundamental Dose Response;24
8.1; Introduction;25
8.2; Historical Antipathies, Rather Than Science, Determined Which DoseResponse Model Would Dominate Biology;26
8.3; The Hormetic Dose-Response Relationship;29
8.4; The Hormesis Database;31
8.5; The Frequency of Hormesis in Toxicology and Pharmacology;39
8.6; Implications of Hormesis;40
8.6.1; Impact on Biological Concepts;41
8.6.1.1; Hormesis Measures Performance;41
8.6.1.2; Hormesis Provides Quantitative Estimates of Biological Plasticity;41
8.6.1.3; Adaptive Response/Preconditioning: Manifestations of Hormesis;42
8.6.1.4; Hormesis as an Expression of Allometry;42
8.7; Toxicological/Pharmacological Implications;43
8.7.1; Factors Affecting the Recognition of Hormetic Dose-Response Relationships;43
8.7.1.1; Use of Multiple Terms;43
8.7.1.2; Modest Stimulation and Historically Weak Study Designs;43
8.7.1.3; Control Group: High Variation;43
8.7.1.4; Low Background Disease Incidence;44
8.7.1.5; Lack of Temporal Component;44
8.7.1.6; Summary;44
8.7.2; Chemical Potency and Hormesis;44
8.7.3; Hormesis: A Novel Concept of Synergy/Potentiation;45
8.7.4; Interindividual Variation and Hormesis;46
8.7.5; Epidemiology and Hormesis;47
8.7.6; Hormesis and Medicine;47
8.7.6.1; Low-Dose Stimulation of Tumor Cells;47
8.7.6.2; Low-Dose Stimulation of Microbes by Antibiotics;48
8.7.6.3; Anxiolytic Drugs;48
8.7.6.4; Antiseizure Drugs;49
8.7.6.5; Memory-Enhancing Drugs;49
8.7.6.6; Stroke Medications;50
8.7.6.7; Osteoporosis;50
8.7.6.8; Hair Growth;51
8.7.6.9; Pulmonary Hypertension;51
8.7.6.10; Fibrotic Diseases (e.g., Dupuytren's Contracture);51
8.7.6.11; Avoidance of Undesirable Side Effects;51
8.7.7; Environmental Risk Assessment;52
8.8; Discussion;59
9;References;60
10;The Fundamental Role of Hormesis in Evolution;66
10.1; Introduction;66
10.2; The Biphasic Dose Response and Evolution;68
10.3; Cellular and Molecular Hormetic Mechanisms;71
10.4; Hormesis and Evolutionary Strategies: Diversification and Specialization;72
10.5; Conclusions and Future Directions;75
11;References;75
12;Transcriptional Mediators of Cellular Hormesis;78
12.1; Introduction;78
12.2; Nature of Transcriptional Regulation;79
12.3; Hormetic Signaling Pathways;80
12.3.1; Nuclear Factor--Erythroid 2p45 (NF-E2)--Related Factor (Nrf2)/Antioxidant Response Element (ARE) Signaling Pathway;81
12.3.2; Nrf2, Keap1, and Regulation of the ARE Pathway;81
12.3.3; Hormetic Inducers of the Nrf2/ARE Pathway;83
12.3.4; Forkhead Box O (FOXO) Transcription Factors;85
12.3.5; FOXO, Oxidative Stress, and Longevity;88
12.3.6; The Nuclear Factor-B Pathway;89
12.3.7; NF-B as a Hormetic Transducer of Exercise;90
12.3.8; Heat-Shock Factor Pathway;91
12.4; Conclusions;95
13;References;96
14;The Devil Is in the Dose: Complexity of Receptor Systemsand Responses;103
14.1; Introduction;103
14.2; Classic and Modern Dynamic GPCR Models;104
14.3; Receptor System Complexities and Responses;106
14.3.1; Multiple G Protein Coupling;106
14.3.2; Allosteric Receptor Modulation;107
14.3.3; Receptor Desensitization;109
14.3.4; Receptor Dimerization;110
14.3.5; GPCRs and Receptorsome Structures;111
14.4; Conclusions;112
15;References;113
16;Exercise-Induced Hormesis;117
16.1; Introduction;117
16.2; Effects of Exercise on the Musculoskeletal System;118
16.2.1; Dose-Response Characteristics of Exercise Effects on Muscle;118
16.2.2; Duration-Dependent Effects of Exercise on Bone;119
16.3; Effects of Exercise on the Digestive System;119
16.3.1; Dose-Dependent Effects of Exercise on the Stomach;119
16.3.2; Hormetic Effects of Exercise in the Large and Small Intestine;119
16.3.3; Dose-Response Characteristics of Exercise Effects on the Liver;119
16.3.4; Duration-Dependent Effects of Exercise on the Pancreas;120
16.4; Effects of Exercise on the Reproductive System;120
16.4.1; Dose-Response Characteristics of Exercise Effects on Ovarian Function;120
16.4.2; Duration-Dependent Effects of Exercise on the Testis;121
16.5; Effects of Exercise on the Cardiorespiratory System;121
16.5.1; Duration-Dependent Effects of Exercise on the Heart;121
16.5.2; Dose-Dependent Effects of Exercise on the Lungs;122
16.6; Effects of Exercise on the Immune System;122
16.6.1; Dose-Response Characteristics of Exercise Effects on the Thymus;122
16.6.2; Hormetic Effects of Exercise on the Spleen;122
16.6.3; Exercise Effects on Circulating Cytokines Conform to the Theory of Hormesis;123
16.7; Effects of Exercise on the Brain;123
16.7.1; Duration-Dependent Effects of Exercise on Adult Neurogenesis;123
16.7.2; Dose-Response Characteristics of Exercise Effects on Dendritic Spines;124
16.7.3; Duration-Dependent Effects on Angiogenesis;125
16.7.4; Duration-Dependent Effects of Running on Neurotrophic Factor Expression;125
16.8; Conclusion;126
17;References;127
18;Dietary Energy Intake, Hormesis, and Health;131
18.1; Introduction;131
18.1.1; CR as a Hormetic Effector;132
18.1.2; CR and Cellular Stress Factors;133
18.1.3; CR Effects Upon Cytokine Levels;134
18.1.4; CR and Alterations in Neurotrophic Factors;135
18.1.5; CR Effects Upon Glycemic Control;135
18.1.6; CR and Satiety/Adipose-Generated Hormones;136
18.1.7; CR and Ketone Body Synthesis;137
18.1.8; CR and Sirtuin Activity;137
18.1.9; CR Modulation of PPARs and Cofactors;138
18.1.10; CR and Transcriptional Regulation;139
18.2; Conclusions;140
19;References;141
20;Couch Potato: The Antithesis of Hormesis;146
20.1; The Couch Potato Caricature;147
20.2; Advances in Technology Reveal the Dangers of a Sedentary Lifestyle;148
20.3; Cellular and Molecular Mechanisms of Exercise Hormesis;148
20.4; Calories In, Disease Out;151
20.5; In One Ear and Out the Other;152
20.6; Implications of Hormesis for the Future of the Couch Potato;154
21;References;154
22;Hormesis and Aging;159
22.1; Introduction;159
22.2; Recapitulating the Biological Basis of Aging;160
22.3; Thermal Hormesis in Aging;163
22.3.1; Thermal Hormesis in Organisms;163
22.3.2; Thermal Hormesis in Human Cells Undergoing Aging in Vitro;164
22.4; Hypergravity Hormesis in Aging;167
22.5; Radiation Hormesis in Aging;167
22.5.1; Radiation Hormesis in Insects;167
22.5.2; Radiation Hormesis in Rodents and Other Animals;168
22.5.3; Radiation Hormesis in Humans;168
22.6; Calorie Restriction and Hormesis;169
22.7; Exercise Hormesis;170
22.8; Nutritional Hormesis and Hormetins;171
22.9; Other Stresses;172
22.10; Hormesis Potential, Challenges, and Unresolved Issues in Aging;173
23;References;175
24;The Hormetic Pharmacy: The Future of Natural Productsand Man-Made Drugs in Disease Prevention and Treatment;182
24.1; Introducing the Pharmacist to Hormesis;182
24.2; Why the Pharmaceutical Industry Is Missing the Hormesis Revolution;183
24.3; Hormesis and Biological Plasticity;184
24.3.1; Dietary Factors;184
24.3.2; Drugs;186
24.4; Implications of the Quantitative Features of the Hormetic Dose Response for the Pharmaceutical and Nutraceutical Worlds;187
24.4.1; Biological Model Selection;187
24.4.2; Drug-Testing Strategies;188
24.4.3; Drug Potency;189
24.4.4; Drug--Drug Interactions;189
24.4.5; Clinical Trials and Hormesis;190
24.5; Potentially Harmful Hormetic Responses;190
24.6; Hormesis in the Pharmaceutical Industry;193
24.6.1; Anxiolytic Drugs;193
24.6.2; Antiseizure Drugs;194
24.6.3; Male Sexual Dysfunction;194
24.6.4; Diabetes;195
24.6.5; Memory/Cognition;195
24.6.6; Osteoporosis;196
24.6.7; Hormesis and Neutraceuticals;196
24.6.8; Hormetic Mimetics;198
24.7; Discussion;199
25;References;200
26;Index;204