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Abstract
Aging is a natural phenomenon that is peculiar to all living things. However, accumulating findings indicate that senescence could be postponed or prevented by certain approaches. Substantial evidence has emerged supporting the possibility of radical human health and lifespan extension, in particular through pharmacological modulation of aging. A number of natural dietary ingredients and synthetic drugs have been assumed to have geroprotective potential. In the development of anti-aging therapeutics, several cell, insect, and animal models may provide useful starting points prior to human studies.
This book provides an overview of current research aimed to search for life-extending medications and describes pharmacological aspects of anti-aging medicine. Readers are introduced to the fascinating historical background of geroprotection in the first chapter. In-depth information on models for investigating geroprotective drugs precedes a section covering anti-aging properties of pharmaceutical compounds, such as calorie restriction mimetics, autophagy inducers, senolytics and mitochondrial antioxidants. Finally, strategies to translate discoveries from aging research into drugs and healthcare policy perspectives on anti-ageing medicine are provided to give a complete picture of the field.
A timely and carefully edited collection of chapters by leading researchers in the field, this book will be a fascinating and useful resource for pharmacologists, gerontologists and any scientifically interested person wishing to know more about the current status of research into anti-aging remedies, challenges and opportunities.
This book would be of interest to a broad audience of scientists who investi-gate mechanisms underlying biological aging and age-related pathologies, medicinal chemists who implement knowledge of these mechanisms into the development of pharmacological geroprotectors for extending human lifespan and healthspan, clinicians who use these geroprotectors to treat various age-related diseases, and medical and university students who study in these fields of research and medical practice. The book would provide fundamental knowledge and thought-provoking new idea in all these fields of research and medical practice.
Professor Vladimir Titorenko, Concordia University, Canada
Alexander Vaiserman was born in KIev, Ukraine, in 1957. He earned his MSc Degree in cytology and developmental biology from Kiev State University in 1984, and his DSc degrees in normal physiology from Instiute of Gerontology (Kiev, Ukraine) in 1991 and 2004, respectively. Since 1978, he has had a permanent position in the Instiute of Gerontology (Kiev, Ukraine). Since 2010, he has been the head of the Laboratory of Epigenetics in the Instiute of Gerontology (Kiev, Ukraine). His research interests comprise epigenetics, epidemiology and experimental gerontology.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Cover | Cover | ||
| Anti-aging Drugs From Basic Research to Clinical Practice | i | ||
| Foreword | vii | ||
| Preface | ix | ||
| Contents | xi | ||
| Section I - Overview | 1 | ||
| Chapter 1 - Anti-Aging Drugs: Where are We and Where are We Going | 3 | ||
| 1.1 Introduction | 3 | ||
| 1.2 Human Life Extension: Concerns and Considerations | 4 | ||
| 1.3 Anti-Aging Pharmacology: Promises and Pitfalls | 5 | ||
| 1.4 Concluding Remarks and Future Directions | 8 | ||
| References | 9 | ||
| Chapter 2 - Aging: Natural or Disease A View from Medical Textbooks | 11 | ||
| 2.1 Introduction | 11 | ||
| 2.1.1 What Does “Aging” Mean | 12 | ||
| 2.1.2 Is Aging a Disease | 12 | ||
| 2.1.2.1 An Attempt at a Broad Account of the Etiology of Senescence | 13 | ||
| 2.1.3 What is an Anti-Aging Intervention | 14 | ||
| 2.1.4 Aims of this Study: How is the Aging vs. Disease Division Represented in Medical Textbooks | 15 | ||
| 2.2 How is Aging Viewed in the Medical Field | 17 | ||
| 2.2.1 Two Surveys of the Medical Perception of Aging | 17 | ||
| 2.2.1.1 BMJ Vote on the Top ‘Non-Diseases’ | 17 | ||
| 2.2.1.2 Surveying the Public, Health Professionals and Legislators on Disease | 18 | ||
| 2.2.2 Medical Textbook Analysis | 18 | ||
| 2.2.2.1 Methodology | 20 | ||
| Textbook Selection.The study was conducted in University College London (UCL) libraries. For the final analysis, 14 textbooks we... | 20 | ||
| The Research Process.To established how the selected textbooks deal with aging, we first reviewed the index for the term aging/a... | 21 | ||
| Strengths and Limitations of the Textbook Analysis.In terms of the textbook selection, this study is limited to textbooks of gen... | 22 | ||
| 2.2.2.2 Results | 23 | ||
| Books Mentioning Aging but Without Dedicated Chapters.Nine textbooks (64.3%) mention aging in the index, of which four dedicate ... | 23 | ||
| Books with Dedicated Chapters on Aging.Of the 14 textbooks, four (28.6%) have a specific chapter on aging. Looking at the number... | 24 | ||
| Summary of Findings.There is considerable variability in the way that aging is represented in textbooks of general clinical medi... | 29 | ||
| 2.3 Discussion | 30 | ||
| Acknowledgements | 32 | ||
| References | 32 | ||
| Chapter 3 - The Search for the “Anti-Aging Pill”: A Critical Viewpoint | 35 | ||
| 3.1 Introduction | 35 | ||
| 3.2 Diverse Life-History Strategies: Consequences for Lifespan Modulation | 37 | ||
| 3.2.1 There Are Various Life-History Strategies in Mammals | 37 | ||
| 3.2.1.1 Only Some Species Increase Their Lifespan When Facing Food Shortage | 39 | ||
| 3.2.1.2 Can Modulating the Insulin–IGF1 Pathway Increase Lifespan in Human Beings | 40 | ||
| 3.2.1.3 Conclusions | 41 | ||
| 3.2.2 The Life-History Strategy of the Nematode Caenorhabditis Elegans Could Explain Why Its Longevity is Plastic | 41 | ||
| 3.3 Toxic and Essential Molecules May Have the Same Effects at Low Doses | 42 | ||
| 3.4 A Drug Treating an Age-Related Pathology is not an “Anti-Aging” Drug | 45 | ||
| 3.5 Conclusions | 45 | ||
| References | 47 | ||
| Section II - Basic Concepts, Models and Approaches | 51 | ||
| Chapter 4 - Testing of Geroprotectors in Experiments on Cell Cultures: Pros and Cons | 53 | ||
| 4.1 Introduction | 53 | ||
| 4.2 Cytogerontological Model Systems | 55 | ||
| 4.3 Constructing of Survival Curves for Cultured Cells in Cytogerontological Experiments | 58 | ||
| 4.4 Interpretation of Data About the Impact of Geroprotectors on Viability of Cultured Cells in Cytogerontological Studies | 63 | ||
| 4.5 Some Words About Biomarkers of Cell Aging/Senescence | 65 | ||
| 4.6 Conclusions | 68 | ||
| References | 70 | ||
| Chapter 5 - Pharmacogenomics and Epigenomics of Age-Related Neurodegenerative Disorders: Strategies for Drug Development | 75 | ||
| 5.1 Introduction | 75 | ||
| 5.2 Age-Related Pheno-Genotypes | 76 | ||
| 5.2.1 Age- and Genotype-Related Phenotype Variation in Common Biochemical and Hematological Parameters | 78 | ||
| 5.2.2 Common Genes with Age-Related Influence on Health Conditions in NDDs | 79 | ||
| 5.3 Pharmacogenomics | 83 | ||
| 5.3.1 APOE-TOMM40 | 95 | ||
| 5.3.2 CYPs | 97 | ||
| 5.3.3 Transporters | 99 | ||
| 5.4 Epigenomics | 100 | ||
| 5.4.1 Age-Related Epigenetics | 101 | ||
| 5.4.1.1 DNA Methylation | 101 | ||
| 5.4.1.2 Histone Modifications | 102 | ||
| 5.4.1.3 Non-Coding RNAs | 103 | ||
| 5.4.2 Neurodegenerative Disorders | 103 | ||
| 5.5 Pharmacoepigenomics | 108 | ||
| 5.6 Novel Strategies | 111 | ||
| 5.6.1 LipoFishins | 123 | ||
| 5.6.1.1 E-SAR-94010 (LipoEsar®) | 123 | ||
| 5.6.1.2 E-JUR-94013 (DefenVid®) | 124 | ||
| 5.6.2 Atremorine (E-PodoFavalin-15999) | 126 | ||
| 5.7 Future Trends for the Management of Age-Related NDDs | 129 | ||
| Acknowledgements | 131 | ||
| References | 131 | ||
| Chapter 6 - Nanotechnology in Anti-Aging: Nutraceutical Delivery and Related Applications | 142 | ||
| 6.1 Introduction | 142 | ||
| 6.2 Nutraceuticals and Nanodevelopments | 143 | ||
| 6.3 Nanoformulations of Bioactive Compounds | 146 | ||
| 6.3.1 Nanoemulsions | 147 | ||
| 6.3.2 Nanoencapsulation/Nanoparticles | 154 | ||
| 6.3.3 Liposomes | 157 | ||
| 6.3.4 Other Nanoformulation Strategies: Nanodisks, Nanogels, Nanofibers etc | 157 | ||
| 6.4 Safety and Regulatory Aspects of Nanofoods | 159 | ||
| 6.5 Consumer Attitude Towards Nanotechnology in Food-Related Applications | 162 | ||
| 6.6 Conclusion | 163 | ||
| References | 164 | ||
| Chapter 7 - Hormetins as Drugs for Healthy Aging | 171 | ||
| 7.1 Introduction | 171 | ||
| 7.2 Aging in a Nutshell | 172 | ||
| 7.3 Hormesis and Stress Response | 173 | ||
| 7.4 Hormetins for Health and Longevity | 175 | ||
| 7.5 Discovering Novel Hormetins | 176 | ||
| 7.6 Drugs for Health and Longevity | 177 | ||
| References | 178 | ||
| Section III - Antioxidants | 181 | ||
| Chapter 8 - Antioxidant Therapy of Aging: From Free Radical Chemistry to Systems Theory of Reliability | 183 | ||
| 8.1 Introduction: Historical Synopsis | 183 | ||
| 8.2 Aging Versus Reliability | 184 | ||
| 8.2.1 Theory of Reliability: Basic Ideas | 184 | ||
| 8.2.2 Preset Reliability Prescribes Lifespan | 185 | ||
| 8.3 Free-Radical Failures | 187 | ||
| 8.3.1 Free-Radical Malfunctions of Electron-Transport Nanoreactors | 187 | ||
| 8.3.2 Free-Radical Redox-Timer of Aging | 189 | ||
| 8.4 Extension of Lifespan by Antioxidants | 191 | ||
| 8.4.1 Antioxidants: Radical Chemistry Standpoint | 191 | ||
| 8.4.2 Antioxidants: Reliability-Theory Standpoint | 195 | ||
| 8.5 Conclusions | 200 | ||
| Acknowledgements | 200 | ||
| References | 201 | ||
| Chapter 9 - Mitochondria-Targeted Rechargeable Antioxidants as Potential Anti-Aging Drugs | 205 | ||
| 9.1 Introduction | 205 | ||
| 9.2 Mitochondria Malfunction and Aging | 206 | ||
| 9.3 The Link Between Oxidative Stress and Aging | 207 | ||
| 9.4 Mitochondria-Targeted Rechargeable Antioxidants | 209 | ||
| 9.4.1 Mitochondria-Targeted Antioxidants in Invertebrate Models | 211 | ||
| 9.4.2 SkQ1 Affects Early Survival and Aging in Unmated Flies | 212 | ||
| 9.4.3 SkQ1 Affects Reproduction in Mated Flies | 213 | ||
| 9.4.4 SkQ1 Acts as a Mitochondria-Targeted Antioxidant Combating ROS in D. melanogaster | 214 | ||
| 9.4.5 SkQ1 Effects are Stable Under Different Experimental Scenarios and Across Different Wild-Type Genotypes | 216 | ||
| 9.5 Mitochondria-Targeted Antioxidants in Rodents | 218 | ||
| 9.6 Conclusion | 220 | ||
| Acknowledgements | 220 | ||
| References | 220 | ||
| Section IV - Mimicking Caloric Restriction | 229 | ||
| Chapter 10 - Mimetics of Caloric Restriction | 231 | ||
| 10.1 Introduction | 231 | ||
| 10.2 Aging and CR | 233 | ||
| 10.2.1 CR in Yeast: Saccharomyces cerevisiae | 233 | ||
| 10.2.2 CR in Worms: Caenorhabditis elegans | 234 | ||
| 10.2.3 CR in Fruit Flies | 235 | ||
| 10.2.4 CR in Mammals | 236 | ||
| 10.3 Beneficial Effects of CR | 238 | ||
| 10.3.1 Cardiovascular System | 238 | ||
| 10.3.2 Brain Function | 239 | ||
| 10.3.3 Hormonal Regulation | 240 | ||
| 10.4 Intracellular Consequences of CR | 241 | ||
| 10.4.1 Autophagy | 242 | ||
| 10.4.2 Metabolism of Reactive Oxygen Species | 243 | ||
| 10.5 Ways to Achieve CR | 244 | ||
| 10.5.1 Decreased Food Consumption | 244 | ||
| 10.5.2 Dietary Composition | 245 | ||
| 10.5.3 Inhibition of Food Digestion and Absorption | 245 | ||
| 10.5.4 Decrease in Appetite and Satiety | 246 | ||
| 10.5.5 Mimetics of CR | 246 | ||
| 10.5.5.1 Biguanides | 246 | ||
| 10.5.5.2 Natural Phenols | 247 | ||
| 10.5.5.3 Rapamycin | 248 | ||
| 10.6 Intracellular Targets of CR | 249 | ||
| 10.6.1 Sensors of Nutrient and Energy State | 249 | ||
| 10.6.2 Signaling Pathways | 250 | ||
| 10.6.2.1 Insulin Signaling Pathway | 251 | ||
| 10.6.2.2 Mechanistic Target-of-Rapamycin (mTOR) Kinase Pathway | 252 | ||
| 10.6.2.3 Nrf2/Keap1 Signaling Pathway | 253 | ||
| 10.7 Conclusion | 255 | ||
| Acknowledgements | 257 | ||
| References | 257 | ||
| Chapter 11 - Allosteric SIRT1 Activators as Putative Anti-Aging Drugs | 272 | ||
| 11.1 Introduction | 272 | ||
| 11.2 The Sirtuin Longevity Pathway | 273 | ||
| 11.3 Small-Molecule SIRT1 Activators | 275 | ||
| 11.4 STACs in Aging and Age-Related Disease | 278 | ||
| 11.4.1 Lifespan Extension | 278 | ||
| 11.4.2 Obesity, Metabolism, and Type II Diabetes | 280 | ||
| 11.4.3 Cancer | 281 | ||
| 11.4.4 Neurodegenerative Disease | 282 | ||
| 11.4.5 Cardiovascular Disease | 282 | ||
| 11.4.6 Inflammation and Immunity | 283 | ||
| 11.4.7 Fertility and Development | 284 | ||
| 11.5 Clinical Challenges with STACs | 285 | ||
| 11.5.1 Pharmacology | 285 | ||
| 11.5.2 Regulatory Paradigms | 286 | ||
| 11.6 Conclusion | 287 | ||
| References | 287 | ||
| Chapter 12 - Therapeutic Potential of Sirtuin Inhibitors in Cancer | 298 | ||
| 12.1 Introduction | 298 | ||
| 12.2 Expression of Sirtuins in Cancer Cells | 299 | ||
| 12.3 Sirtuins and the Hallmarks of Cancer | 301 | ||
| 12.4 Sirtuin Inhibitors as Anticancer Agents | 306 | ||
| 12.4.1 Nicotidamine and Its Analogues | 306 | ||
| 12.4.2 Splitomicin and Its Derivatives | 308 | ||
| 12.4.3 Sirtinol | 309 | ||
| 12.4.4 Cambinol | 310 | ||
| 12.4.5 Salermide | 313 | ||
| 12.4.6 Indole Derivatives | 313 | ||
| 12.4.7 Tenovin | 314 | ||
| 12.4.8 Other Inhibitors of Human Sirtuins | 317 | ||
| 12.5 Concluding Remarks | 319 | ||
| Acknowledgements | 319 | ||
| References | 319 | ||
| Chapter 13 - Lifespan-Extending Effect of Resveratrol and Other Phytochemicals | 328 | ||
| 13.1 Introduction | 328 | ||
| 13.2 Resveratrol | 329 | ||
| 13.2.1 Lifespan-Extending Effect of Resveratrol in Invertebrates: Yeasts, Worms and Flies | 329 | ||
| 13.2.2 Lifespan-Extending Effects of Resveratrol in Vertebrate: Fishes and Rodents | 331 | ||
| 13.2.3 Clinical Trials of Resveratrol in Human Subjects | 332 | ||
| 13.2.4 Putative Target Molecules for Lifespan-Extending Effect of Resveratrol | 333 | ||
| 13.2.4.1 Caloric Restriction Mimetics | 333 | ||
| 13.2.4.2 NAD+-Dependent Deacetylase Sirtuin | 334 | ||
| 13.2.4.3 Autophagy | 335 | ||
| 13.2.4.4 Other Molecular Targets | 336 | ||
| 13.2.5 Uncertainty of Resveratrol as a Clinical Drug | 336 | ||
| 13.3 Other Phytochemicals with Lifespan-Extending Effects | 337 | ||
| 13.3.1 Curcumin | 337 | ||
| 13.3.2 Quercetin | 339 | ||
| 13.3.3 Catechin | 339 | ||
| 13.3.4 Others | 340 | ||
| 13.4 Conclusion | 342 | ||
| References | 342 | ||
| Chapter 14 - Extending Lifespan by Inhibiting the Mechanistic Target of Rapamycin (mTOR) | 352 | ||
| 14.1 The Discovery of Rapamycin and mTOR | 352 | ||
| 14.2 mTOR Regulates Longevity in Model Organisms | 354 | ||
| 14.3 Rapamycin Extends the Lifespan and Healthspan of Mice | 355 | ||
| 14.4 How Does Rapamycin Increase Longevity | 358 | ||
| 14.5 Side Effects of Rapamycin Treatment—The Role of mTORC2 | 359 | ||
| 14.6 mTORC1 Is a Key Integrator of Nutrient and Hormonal Signaling | 360 | ||
| 14.7 How Can mTORC1 Be Specifically Targeted | 362 | ||
| 14.8 Conclusions | 365 | ||
| Acknowledgements | 365 | ||
| References | 366 | ||
| Chapter 15 - mTOR, Aging and Cancer: Prospects for Pharmacological Interventions | 376 | ||
| 15.1 Rapamycin: A Brief History | 376 | ||
| 15.2 The Target of Rapamycin | 377 | ||
| 15.3 Rapamycin’s Mysterious Effects on Aging | 379 | ||
| 15.4 Effects of Chronic Rapamycin on Age-Associated Diseases | 379 | ||
| 15.5 TOR Reductions and Rapamycin Increase Longevity in Other Organisms | 382 | ||
| 15.6 Genetic mTOR Inhibition in Mice that Extends Life Span | 383 | ||
| 15.7 Composite Picture of mTOR Signaling Pathways in Aging | 383 | ||
| 15.8 Why This Is Important | 385 | ||
| 15.9 Summary | 386 | ||
| Potential Financial Conflict of Interest | 387 | ||
| Acknowledgements | 387 | ||
| References | 387 | ||
| Chapter 16 - Anti-Aging Action of PPARs: Potential Therapeutic Targets | 393 | ||
| 16.1 Introduction | 393 | ||
| 16.2 Age-Related Changes in Inflammation and Their Role in Metabolic Diseases | 394 | ||
| 16.2.1 Chronic Inflammation and Aging | 394 | ||
| 16.2.2 Roles of Inflammation in Metabolic Diseases During Aging | 395 | ||
| 16.3 Functions of PPARs in the Regulation of Metabolism and Inflammation | 396 | ||
| 16.3.1 PPAR Signaling and Metabolism | 396 | ||
| 16.3.2 PPARs and Inflammation | 398 | ||
| 16.4 Evidence for Involvement of PPARs in Age-Related Inflammatory Diseases and Aging | 400 | ||
| 16.4.1 The Role of PPARs in Age-Related Inflammatory Diseases | 401 | ||
| 16.4.1.1 Atherosclerosis and Cardiovascular Diseases | 401 | ||
| 16.4.1.2 Alzheimer’s Disease | 402 | ||
| 16.4.1.3 Inflammatory Bowel Diseases | 402 | ||
| 16.4.2 PPARs in Aging and Longevity | 403 | ||
| 16.5 Anti-Aging and Therapeutic Potentials of New PPAR Agonists | 404 | ||
| 16.6 Effects of Anti-Aging Calorie Restriction on PPAR Modulation | 406 | ||
| 16.7 Conclusion | 407 | ||
| References | 408 | ||
| Chapter 17 - Antidiabetic Biguanides as Anti-Aging Drugs | 416 | ||
| 17.1 Introduction | 416 | ||
| 17.2 Milestones in Research on Biguanides as Drugs for Aging Prevention in Rodents | 417 | ||
| 17.3 Effect of Antidiabetic Biguanides on Aging and Life Span in Rats | 418 | ||
| 17.4 Effect of Antidiabetic Biguanides on Aging and Life Span in Mice | 420 | ||
| 17.5 Antidiabetic Biguanides in Prevention of Age-Associated Diseases in Mouse Models | 424 | ||
| 17.6 Antidiabetic Biguanides as Anti-Carcinogens and Inhibitors of Tumor Growth in Rodents | 424 | ||
| 17.7 Conclusion | 427 | ||
| Acknowledgement | 429 | ||
| References | 429 | ||
| Section V - Other Pharmacological Approaches | 433 | ||
| Chapter 18 - S-Adenosylmethionine Metabolism: A Promising Avenue in Anti-Aging Medicine | 435 | ||
| 18.1 Introduction | 435 | ||
| 18.1.1 Discovery of S-Adenosylmethionine | 435 | ||
| 18.1.2 SAM and Aging | 436 | ||
| 18.1.3 This Review | 437 | ||
| 18.2 SAM-Dependent Enzymes | 437 | ||
| 18.2.1 Parts of SAM Used by SAM-Dependent Enzymes | 437 | ||
| 18.2.2 Structures of SAM-Dependent Enzymes | 438 | ||
| 18.3 Well-Known Pathways of SAM in Central Metabolism | 438 | ||
| 18.3.1 The Methionine Cycle | 438 | ||
| 18.3.2 The Transsulfuration Pathway to Glutathione | 442 | ||
| 18.3.3 The Polyamine Pathway | 442 | ||
| 18.4 SAM and RNA-Based Control by Riboswitches | 443 | ||
| 18.4.1 Discovery of SAM Riboswitches | 443 | ||
| 18.4.2 SAM and Other Riboswitches | 443 | ||
| 18.5 ‘Radical SAM’ Proteins with Iron–Sulfur (FeS) Clusters | 444 | ||
| 18.5.1 Discovery of Radical SAM Enzymes | 444 | ||
| 18.5.2 The Radical SAM-Binding Domain | 444 | ||
| 18.5.3 Types of SAM Radical Enzymes | 445 | ||
| 18.5.4 Radical SAM Methyltransferases (RSMT) | 446 | ||
| 18.5.5 Radical SAM Methylthiotransferases (MMTases) | 447 | ||
| 18.5.6 The Special Case of Elp3 | 447 | ||
| 18.5.7 Lessons from SAM-Independent FeS Proteins | 448 | ||
| 18.6 SAM and Aging | 449 | ||
| 18.6.1 SAM, Mitochondria and Aging | 449 | ||
| 18.6.2 SAM and Neurodegeneration | 449 | ||
| 18.6.3 SAM and Long-Lived Rodents | 450 | ||
| 18.6.4 SAM, the Microbiome and Aging | 450 | ||
| 18.6.5 SAM and Establishment and Maintenance of the Microbiome | 451 | ||
| 18.7 Conclusions | 452 | ||
| Note Added after Completion of the Manuscript | 453 | ||
| Abbreviations | 453 | ||
| References | 454 | ||
| Chapter 19 - Melatonin as a Geroprotector: Healthy Aging vs. Extension of Lifespan | 474 | ||
| 19.1 Introduction | 474 | ||
| 19.2 Overview of Melatonin’s Actions in Relation to Aging | 477 | ||
| 19.2.1 Energy Balance and Metabolic Sensing | 477 | ||
| 19.2.2 Counter-Action of Mitochondrial Dysfunction and Anti-Oxidant Actions | 481 | ||
| 19.2.3 Immunological Actions and Prevention of Inflammaging | 483 | ||
| 19.2.4 Telomere Attrition | 486 | ||
| 19.3 Lifespan, Health, Deceleration and Deacceleration of Aging | 486 | ||
| 19.4 Conclusion | 488 | ||
| References | 489 | ||
| Chapter 20 - Short Peptides Regulate Gene Expression, Protein Synthesis and Enhance Life Span | 496 | ||
| 20.1 Introduction | 496 | ||
| 20.2 Isolated Peptide Complexes | 498 | ||
| 20.3 Short Synthetic Peptides | 500 | ||
| 20.4 Influence of Short Peptides on Immune and Antioxidant Systems | 501 | ||
| 20.5 The Influence of Short Peptides on Gene Expression | 503 | ||
| 20.6 Application of Peptide Bioregulators in Elderly Patients | 504 | ||
| 20.7 Prospective Cellular and Molecular Mechanism of Action of Short Peptides | 507 | ||
| 20.8 Conclusion | 509 | ||
| References | 510 | ||
| Chapter 21 - HDAC Inhibitors: A New Avenue in Anti-Aging Medicine | 514 | ||
| 21.1 Introduction | 514 | ||
| 21.2 Role of Histone Modification in Epigenetic Regulation | 516 | ||
| 21.3 Life Span-Modulating Effects of HDAC Inhibitors in Animal Models | 517 | ||
| 21.3.1 Phenylbutyrate | 518 | ||
| 21.3.2 Sodium Butyrate | 519 | ||
| 21.3.3 Trichostatin A | 523 | ||
| 21.3.4 Suberoylanilide Hydroxamic Acid (SAHA) | 525 | ||
| 21.4 HDACIs in Preclinical and Clinical Trials | 526 | ||
| 21.4.1 Cancer | 527 | ||
| 21.4.2 Metabolic and Cardiovascular Pathology | 527 | ||
| 21.4.3 Neurodegenerative Diseases | 528 | ||
| 21.4.4 Inflammatory Disorders | 528 | ||
| 21.5 Conclusion | 529 | ||
| Acknowledgements | 529 | ||
| References | 529 | ||
| Section VI - Social Context | 535 | ||
| Chapter 22 - Human Life Extension: Opportunities, Challenges, and Implications for Public Health Policy | 537 | ||
| 22.1 Introduction: The Diverse Aspects of Life Extension Promotion as a Part of Health Promotion | 537 | ||
| 22.2 Scientific and Technological Implications and Challenges: Is Human Life Extension Scientifically and Technologically Feasibl... | 540 | ||
| 22.3 Implications and Challenges for the Individual and the Society: Is Life Extension a Desirable Goal | 545 | ||
| 22.4 Normative Action: What Should We Do | 551 | ||
| 22.4.1 Funding | 552 | ||
| 22.4.2 Incentives | 554 | ||
| 22.4.3 Institutional Support | 557 | ||
| References | 559 | ||
| Subject Index | 565 |