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E-raamat: Epigenetics of Aging and Longevity: Translational Epigenetics vol 4

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Edited by Alexey Moskalev (Head of the Laboratory of Molecular Radiobiology and Gerontology, Institute of Biology, Komi Science Center of RAS, Syktyvkar, Russia), Edited by Alexander Vaiserman (Head of the Laboratory of Epigenetics, Institute of Gerontology, Kiev, Ukraine)

Formaat: EPUB+DRM
Sari: Translational Epigenetics
Ilmumisaeg: 17-Nov-2017
Kirjastus: Academic Press Inc
Keel: eng
ISBN-13: 9780128110836

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Formaat: EPUB+DRM
Sari: Translational Epigenetics
Ilmumisaeg: 17-Nov-2017
Kirjastus: Academic Press Inc
Keel: eng
ISBN-13: 9780128110836

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Epigenetics of Aging and Longevity provides an in-depth analysis of the epigenetic nature of aging and the role of epigenetic factors in mediating the link between early-life experiences and life-course health and aging. Chapters from leading international contributors explore the effect of adverse conditions in early-life that may result in disrupted epigenetic pathways, as well as the potential to correct these disrupted pathways via targeted therapeutic interventions. Intergenerational epigenetic inheritance, epigenetic drug discovery, and the role of epigenetic mechanisms in regulating specific age-associated illnesses—including cancer and cardiovascular, metabolic, and neurodegenerative diseases—are explored in detail.

This book will help researchers in genomic medicine, epigenetics, and biogerontology better understand the epigenetic determinants of aging and longevity, and ultimately aid in developing therapeutics to extend the human life-span and treat age-related disease.

Offers a comprehensive overview of the epigenetic nature of aging, as well as the impact of epigenetic factors on longevity and regulating age-related disease
Provides readers with clinical and epidemiological evidence for the role of epigenetic mechanisms in mediating the link between early-life experiences, life-course health and aging trajectory
Applies current knowledge of epigenetic regulatory pathways towards developing therapeutic interventions for age-related diseases and extending the human lifespan

List of Contributors

xix

Preface

xxiii

SECTION 1 EPIGENETIC MECHANISMS IN AGING

Chapter 1 Aging Epigenetics: Changes and Challenges

(30)

Duygu Ucar

Berenice A. Benayoun

1 Introduction

(1)

2 Epigenetic Alterations and the Aging Process

(6)

2.1 The `Aging Epigenome'

(6)

2.2 Impact of Environmental Stimuli on the Aging Epigenome

(1)

3 Significance of the Aging Epigenome

(2)

3.1 Age-Related Loss of Transcriptional Precision

(1)

3.2 Links Between Epigenetic and Genomic Instability With Age

(1)

4 The Power of Genomics: Global Versus Genome-Wide Locus-Specific Age-Related Changes

(3)

4.1 DNA-Methylation Profiling in Aged Human Cells

(1)

4.2 Lessons From Genome-Wide Profiling of Chromatin Landscape With Aging...

(1)

4.3 Advances in Epigenome Profiling in Human Cells

(1)

5 Emerging Challenges in the Field of Aging Epigenomics

(4)

5.1 Toward Epigenetic Longevity Drugs?

(1)

5.2 Sex-Dimorphism and Implications

(1)

5.3 Epigenomics of Immune System Aging

(1)

5.4 The Challenges of Multiomic Data Integration and Interpretation

(1)

5.5 Accounting for Cell Intrinsic Versus Cell Composition-Derived Changes With Epigenomic Aging

(1)

6 Conclusions

(13)

List of Acronyms and Abbreviations

(1)

Glossary

(1)

Acknowledgments

(1)

References

(11)

Chapter 2 Defective DNA Methylation/Demethylation Processes Define Aging-Dependent Methylation Patterns

(26)

Michele Zampieri

Fabio Ciccarone

Paola Caiafa

1 Introduction

(1)

2 DNA Methylation/Demethylation in Mammals

(5)

2.1 DNA Methylation Processes

(2)

2.2 Distribution of the DNA Methylation Signal in the Genome

(1)

2.3 DNA Demethylation Processes

(1)

2.4 Distribution of the 5hmC Signal in the Genome

(1)

3 Effect of Environmental Factors on DNA Epigenetic Modifications

(1)

4 The Impact of Aging on DNA Epigenetic Modification Patterns

(3)

4.1 Age-Associated DNA Hypomethylation

(1)

4.2 Age-Associated DNA Hypermethylation

(1)

4.3 The "Epigenetic Clock"

(1)

4.4 DNA Hydroxymethylation in Aging

(1)

5 Toward Molecular Mechanisms for the Aging-Related Changes of DNA Epigenetic Modification Patterns

(5)

6 Conclusions

(11)

List of Abbreviations

(2)

Glossary

(1)

References

(8)

Chapter 3 S-Adenosylmethionine Metabolism and Aging

(36)

Wil A.M. Loenen

1 Introduction

(2)

2 This Review

(1)

3 Well-Known Pathways of SAM in Central Metabolism

(1)

3.1 The Methionine Cycle

(1)

3.2 The Transsulfuration Pathway to GSH

(1)

3.3 The Polyamine Cycle

(1)

4 SAM and RNA-Based Control by Riboswitches

(1)

5 Radical SAM Proteins With Iron-Sulfur (FeS) Clusters

(4)

5.1 FeS Proteins

(1)

5.2 SAM-Dependent Radical FeS Proteins

(1)

5.3 Types of Radical SAM Enzymes

(1)

5.4 Radical SAM Enzymes in Human Disease

(1)

5.5 Radical SAM Enzymes That Modify Mammalian tRNAs

(1)

5.6 Radical SAM Methyltransferases and MMTases

(1)

6 SAM and Its Role in Aging and Longevity

(3)

6.1 SAM, Mitochondria, and Aging

(1)

6.2 SAM and Neurodegeneration

(1)

6.3 SAM and Long-Lived Rodents

(1)

6.4 SAM, the Microbiome and Aging

(1)

6.5 SAM and the Establishment and Maintenance of the Microbiome

(1)

7 Conclusion

(24)

List of Abbreviations

(1)

References

(22)

Chapter 4 The Epigenetic Clock and Aging

(24)

Ken Raj

1 Introduction

(1)

2 Global DNA Methylation Changes in Function of Age

(1)

3 Site-Specific DNA Methylation Changes in Function of Age

(2)

4 The Epigenetic Clock

(1)

5 Desynchronization of Epigenetic Age From Chronological Age

(5)

5.1 Aging Abnormalities

(1)

5.2 Neurological Disorders

100

(1)

5.3 Hormones

101

(1)

5.4 Obesity and Diet

101

(1)

5.5 Viral Infection

102

(1)

5.6 Cancers

103

(1)

5.7 Induction of Pluripotency

103

(1)

6 Epigenetic Age and Mortality

104

(1)

7 The Epigenetic Aging of In Vitro-Cultured Cells

104

(1)

8 The Epigenetic Clock at the Cellular Level

105

(3)

8.1 How the Clock Ticks

106

(1)

8.2 The Legacy of Life

107

(1)

9 Epigenetic Aging and Cellular Senescence

108

(1)

10 Epigenetic Aging, Telomere, and Telomerase

109

(1)

11 Two Routes to Aging

109

(2)

12 Conclusion

111

(8)

List of Acronyms and Abbreviations

112

(1)

Glossary

113

(1)

References

113

(6)

Chapter 5 The Epigenetic Regulation of Telomere Maintenance in Aging

119

(18)

Huda Adwan-Shekhidem

Gil Atzmon

1 Introduction

119

(1)

2 Epigenetics of Aging and Longevity

120

(1)

3 The Epigenetic Aging Clock

121

(1)

4 Telomeres and Aging

122

(1)

4.1 Telomere Structure

122

(1)

4.2 Telomerase Structure

122

(1)

5 Telomere Attrition as an Aging Hallmark

122

(2)

6 Shelterin Complex and Telomerase Enzyme in Aging

124

(1)

7 Telomere Length and Longevity

125

(1)

8 Animal Models in Telomeres and Aging Studies

125

(1)

9 Epigenetics and Telomeres

126

(1)

9.1 Telomere Maintenance

126

(1)

9.2 Epigenetic Regulation of Telomeres

126

(1)

10 Epigenetic Modifications in Telomeres

127

(2)

10.1 Histone Modifications

127

(1)

10.2 DNA Methylation

128

(1)

10.3 RNA Interference

128

(1)

11 Telomeres as Epigenetic Agents

129

(1)

12 Epigenetics of Aging and Its Relevance to Telomere Length

129

(1)

13 Conclusion

130

(7)

List of Acronyms and Abbreviations

131

(1)

Glossary

131

(1)

References

131

(6)

Chapter 6 Living Long and Aging Well: Are Lifestyle Factors the Epigenetic Link in the Longevity Phenotype?

137

(16)

Irene M. Rea

Ken I. Mills

1 Introduction

137

(2)

2 Keeping Physically Active

139

(2)

2.1 Exercise as an Epigenetic Modifier

139

(1)

2.2 Muscles Are Remodeled

139

(1)

2.3 Exercise Revitalizes Mitochondria

140

(1)

3 Maintaining Good Mental Activity

141

(2)

3.1 The Brain--Exercise Epigenetic Link

141

(1)

3.2 Brain-Derived Neurotrophic Factor

142

(1)

4 Eating Well

143

(2)

4.1 Diet and Epigenetics

143

(2)

4.2 Calorie Intake and Epigenetics

145

(1)

5 Conclusion

145

(8)

List of Abbreviations

147

(1)

Acknowledgments

148

(1)

References

148

(5)

Chapter 7 Epigenetic Biomarkers for Biological Age

153

(18)

Arnold B. Mitnitski

1 Introduction: Biological Age is a Metaphor for Heterogeneity of Health of People at the Same Chronological Age

154

(1)

2 Multiple Biological Markers (Battery of Biomarkers) as Age Predictors

155

(1)

3 Estimation of Biological Age

156

(1)

4 Epigenetic Methylation Markers---DNA Methylation Level Changes With Age

157

(1)

5 DNAm Age of Horvath

157

(2)

6 DNAm Age of Hannum

159

(1)

7 DNAm Age of Weidner

160

(1)

8 Delta Age--Age Acceleration

160

(1)

8.1 Gestational Age

161

(1)

9 Morbidity, DNAm Age, and Age Acceleration

161

(2)

9.1 Alzheimer's Disease

161

(1)

9.2 Parkinson's Disease

161

(1)

9.3 Insomnia

161

(1)

9.4 Lung Cancer

161

(1)

9.5 Osteoarthritis (OA)

162

(1)

9.6 Cognitive Impairment

162

(1)

9.7 Reproductive Function in Women

162

(1)

9.8 Coronary Heart Diseases

162

(1)

9.9 Down Syndrome (DS)

162

(1)

9.10 Cerebellum Aging

163

(1)

9.11 Posttraumatic Stress Disorder (PTSD)

163

(1)

9.12 Huntington's Disease (HD)

163

(1)

9.13 HIV

163

(1)

10 DNAm Age in Semisupercentenarians

163

(1)

11 Clinical Use: Perspectives

164

(1)

12 DNAm Age and Frailty

164

(1)

13 DNAm Age and Mortality

165

(1)

14 Biological Age: One or Many?

166

(1)

15 Conclusion

167

(4)

List of Acronyms and Abbreviations

167

(1)

References

167

(4)

Chapter 8 The Role of Noncoding RNAs in Genome Stability and Aging

171

(30)

Igor Kovalchuk

1 Introduction

172

(1)

2 Genomic DNA Elimination in Ciliates

172

(1)

3 The Regulation of Genome Stability Through miRNAs

173

(4)

3.1 An Indirect Role of miRNAs in Genome Stability

173

(1)

3.2 DNA Repair Proteins Regulate miRNA Biogenesis

173

(3)

3.3 miRNAs Regulate the Activity of DNA Damage Sensors and Effectors

176

(1)

4 The Role of piRNAs in the Integrity of the Genome in the Germline

177

(5)

4.1 piRNAs in Drosophila

177

(4)

4.2 piRNAs in Mammals

181

(1)

4.3 piRNAs in Transgenerational Response

181

(1)

5 The Maintenance of Genome Stability by Small Interfering RNAs

182

(6)

5.1 siRNAs in Neurospora crassa

182

(2)

5.2 Small ncRNAs Induced by DNA Strand Breaks in Mammals and Plants

184

(4)

6 The Role of ncRNAs in Aging

188

(5)

6.1 The Role of miRNAs in Aging

188

(2)

6.2 The Role of IncRNA in Aging

190

(3)

6.3 Extracellular RNAs in Aging

193

(1)

7 Conclusion

193

(8)

List of Abbreviations

194

(1)

Glossary

194

(1)

References

195

(6)

Chapter 9 Intratissue DNA Methylation Heterogeneity in Aging

201

(12)

Jan Vijg

Silvia Gravina

Xiao Dong

1 Introduction

201

(1)

2 Changes in DNA Methylation in Cancer

202

(1)

3 Changes in DNA Methylation in Aging

203

(1)

4 Stochastic Changes in DNA Methylation

203

(4)

5 Conclusion

207

(6)

Acknowledgments

208

(1)

References

208

(5)

SECTION 2 EARLY-LIFE EPIGENETIC PROGRAMMING OF AGING TRAJECTORIES

Chapter 10 Early-Life Nutrition, Epigenetics, and Altered Energy Balance Later in Life

213

(16)

Clare M. Reynolds

Justin M. O'Sullivan

Stephanie A. Segovia

Mark H. Vickers

1 Introduction

213

(7)

1.1 Programming of Altered Energy Balance: Human Evidence

215

(1)

1.2 Programming of Altered Energy Balance: Evidence From Animal Models

215

(5)

2 Interventions

220

(1)

3 Conclusions

221

(8)

List of Acronyms arid Abbreviations

222

(1)

Glossary

222

(1)

References

222

(7)

Chapter 11 Early Nutrition, Epigenetics, and Human Health

229

(22)

Simon C. Langley-Evans

Beverly S. Muhlhausler

1 The Early-Life Origins of Disease

229

(2)

2 The Impact of Undernutrition

231

(3)

3 The Impact of Overnutrition

234

(3)

4 The Contribution of Epigenetics

237

(6)

5 Summary and Conclusions

243

(8)

List of Abbreviations

244

(1)

Glossary

244

(1)

References

245

(5)

Further Reading

250

(1)

Chapter 12 Biological Embedding of Psychosocial Stress Over the Life Course

251

(20)

Helen Eachus

Vincent T. Cunliffe

1 Introduction

251

(3)

2 Maladaptive Stress Responses Are Engendered by Persistent Exposure to Stressors

254

(2)

3 The Social Gradient in Health: Role of Low Socioeconomic Status in Epigenetic Embedding of Biological Stress

256

(1)

4 Glucocorticoid Resistance, Hypercortisolism, and Depression

257

(2)

5 Posttraumatic Stress Disorder and Epigenetic Modulation of Sensitivity to Trauma

259

(1)

6 Hypercortisolism Syndromes and Their Epigenetic Impacts on Mental Health

259

(1)

7 Chronic Stress and Its Impacts on Epigenetic Age Acceleration

260

(1)

8 Conclusions and Future Perspectives

261

(10)

Acknowledgments

264

(1)

References

264

(7)

Chapter 13 Epigenetics of Longevity in Social Insects

271

(22)

Alexander M. Vaiserman

Oleh V. Lushchak

Alexander K. Koliada

1 Introduction

271

(2)

2 Epigenetics of Caste Differentiation

273

(8)

2.1 DNA Methylation

273

(3)

2.2 Alternative Splicing

276

(1)

2.3 Histone Modifications

276

(1)

2.4 Micro-RNAs

277

(1)

2.5 Caste-Specific Differences in Gene Expression Patterns

278

(3)

3 Interplay Between Epigenetic and Endocrine Factors in Regulation of Longevity in Social Insects

281

(3)

4 Conclusions and Future Perspectives

284

(9)

Acknowledgment

285

(1)

References

285

(8)

SECTION 3 EPIGENETICS OF AGING-ASSOCIATED DISEASES

Chapter 14 Drosophila melanogaster as a Model for Studying the Epigenetic Basis of Aging

293

(16)

Ilya Solovev

Mikhail Shaposhnikov

Anna Kudryavtseva

Alexey Moskalev

1 Introduction

293

(1)

2 Age-Related Chromatin Changes in D. melanogaster

294

(4)

2.1 DNA Methylation

294

(1)

2.2 Histone Methylation

295

(1)

2.3 Histone Acetylation and Associated Processes

296

(1)

2.4 Determination of Lifespan by Histone Deacetylases

297

(1)

2.5 Nucleosome Remodeling

297

(1)

3 Premature Aging Models

298

(1)

4 The Role of Transposable Elements in Drosophila Aging

299

(1)

5 Environmental and Nutritional Impacts on Aging, Stress-Resistance, and Longevity

300

(1)

6 Pharmacological Interventions in Drosophila Aging

301

(1)

7 Conclusions and Perspectives

302

(7)

References

302

(7)

Chapter 15 Histone Modification Changes During Aging: Cause or Consequence?---What We Have Learned About Epigenetic Regulation of Aging From Model Organisms

309

(20)

Xiaohua Cao

Weiwei Dang

1 Introduction

310

(1)

2 Histone Posttranslational Modifications

310

(5)

2.1 Histone Acetylation

311

(1)

2.2 Histone Methylation

312

(1)

2.3 Histone Phosphorylation

313

(2)

2.4 Histone Ubiquitylation and Sumoylation

315

(1)

3 Histone Modifications Change During Aging, From Yeast to Humans

315

(7)

3.1 Age-Related Histone Acetylation

315

(4)

3.2 Age-Related Histone Methylation Changes

319

(3)

4 Concluding Remarks

322

(7)

Acknowledgments

322

(1)

References

323

(6)

Chapter 16 Epigenetics of Brain/Cognitive Aging

329

(18)

Xiangru Xu

1 Brain/Cognitive Aging

329

(2)

2 DNA Methylation, Brain Aging, and Cognitive Impairment

331

(4)

2.1 DNA Methylation

331

(2)

2.2 DNA Methylation and Brain/Cognitive Aging

333

(2)

3 Histone Posttranslational Modifications and Brain/Cognitive Aging

335

(2)

3.1 Histone Posttranslational Modifications

335

(1)

3.2 Histone Posttranslational Modifications and Brain/Cognitive Aging

336

(1)

4 Effective Interventions and Drug Development Targeting Epigenetic Marks in Brain/Cognitive Aging

337

(2)

4.1 Effective Interventions

337

(1)

4.2 Epigenetic Drug Development

338

(1)

5 Perspectives and Challenges

339

(8)

List of Acronyms and Abbreviations

341

(1)

References

341

(6)

Chapter 17 The Role of Epigenetic Modifications in Cardiometabolic Diseases

347

(18)

Kim V.E. Braun

Eliana Portilla

Rajiv Chowdhury

Jana Nano

Jenna Troup

Trudy Voortman

Oscar H. Franco

Taulant Muka

1 Introduction

348

(1)

2 Epigenetics and Dyslipidemia

348

(2)

2.1 Global DNA Methylation

348

(1)

2.2 DNA Methylation in Candidate Genes

349

(1)

2.3 Epigenome-Wide Association Studies

349

(1)

3 Epigenetics and Inflammation

350

(1)

3.1 DNA Methylation

350

(1)

3.2 Histone Modifications

351

(1)

4 Epigenetics and Subclinical Atherosclerosis

351

(1)

4.1 DNA Methylation

351

(1)

4.2 Histone Modifications

352

(1)

5 Epigenetics, Glycemic Traits, and Type II Diabetes

352

(2)

5.1 Global DNA Methylation

352

(1)

5.2 Candidate Gene Studies

353

(1)

5.3 Epigenome-Wide Analysis

353

(1)

5.4 Histone Modifications

353

(1)

6 Epigenetics and Cardiovascular Disease

354

(1)

6.1 DNA Methylation

355

(1)

6.2 Histone Modifications

355

(1)

7 Discussion

355

(3)

7.1 Global DNA Methylation and Cardiometabolic Disease

356

(1)

7.2 Epigenome-Wide Association Studies, Candidate Gene Approach, and Cardiometabolic Disease

357

(1)

8 Conclusion

358

(7)

List of Abbreviations

359

(1)

References

359

(6)

Chapter 18 Epigenetic Mechanisms in Osteoporosis

365

(24)

Barbara Ostanek

Tilen Kranjc

Nika Lovsin

Janja Zupan

Janja Marc

1 Introduction

365

(5)

2 DNA Methylation in Osteoporosis

370

(4)

3 Histone Modifications in Osteoporosis

374

(2)

4 MicroRNAs in Osteoporosis

376

(4)

5 Long Noncoding RNAs in Osteoporosis

380

(1)

6 Interaction Between Epigenetic Mechanisms in Osteoporosis

380

(1)

7 Conclusions

381

(8)

List of Acronyms and Abbreviations

382

(2)

Acknowledgments

384

(1)

References

384

(5)

Chapter 19 Epigenetics of Skeletal Muscle Aging

389

(30)

Adam P. Sharples

Robert A. Seaborne

Claire E. Stewart

1 Introduction and Overview: Age-Related Muscle Loss/Sarcopenia

389

(2)

2 Programming and Early-Life Origins of Longevity and Health in Aging Skeletal Muscle

391

(3)

2.1 Molecular Mechanisms of Nutrient Programming in Skeletal Muscle

391

(2)

2.2 Epigenetic Regulation of Skeletal Muscle Nutrient Programming

393

(1)

3 Epigenetics of Aging in Skeletal Muscle Stem Cell Proliferation, Differentiation, Regeneration and Self-Renewal

394

(7)

3.1 Role of Satellite Cells in Aging Skeletal Muscle Repair and Regeneration

394

(1)

3.2 Extracellular/Intracellular Signal Transduction and Transcriptional Control of Satellite Cell Myogenesis and Self-Renewal

394

(2)

3.3 Epigenetic Regulation of Adult Myogenesis

396

(1)

3.4 Epigenetic Regulation of Aging Skeletal Muscle Satellite Cells During Myogenesis

397

(2)

3.5 Inflammation and Epigenetics in Aging Skeletal Muscle Myogenesis

399

(1)

3.6 External Niche in Skeletal Muscle Stem Cell Aging

400

(1)

4 Skeletal Muscle Has an `Epigenetic Memory' Across the Lifespan

401

(4)

5 Conclusion

405

(14)

References

405

(14)

SECTION 4 EPIGENOME-TARGETED THERAPIES IN GEROCSCIENCE

Chapter 20 Healthy Aging and Epigenetic Drugs for Diabetes and Obesity: A Novel Perspective

419

(20)

Sunitha Meruvu

John D. Bowman

Mahua Choudhury

1 Introduction

419

(1)

2 Epigenetics in Diabetes, Obesity, and Aging

420

(1)

3 DNA Methylation

421

(1)

4 Histone Modifications

422

(1)

5 Noncoding RNAs

423

(1)

6 Epigenetic Drugs

424

(7)

6.1 Histone Deacetylase Inhibitors

424

(2)

6.2 Valproic Acid

426

(1)

6.3 Sodium Butyrate

427

(1)

6.4 Sodium Phenylbutyrate

427

(1)

6.5 Vorinostat

428

(1)

6.6 Histone Acetyltransferase Inhibitors

428

(1)

6.7 Sirtuin-Activating Compounds

429

(1)

6.8 Metformin

430

(1)

6.9 Melatonin

430

(1)

7 Conclusion

431

(8)

Acknowledgments

431

(1)

References

431

(8)

Chapter 21 Epigenetic Drugs for Cancer and Precision Medicine

439

(14)

Mukesh Verma

Vineet Kumar

1 Introduction

439

(4)

2 DNA Methyltransferase Inhibitors

443

(1)

3 Histone Deacetylase Inhibitors

444

(1)

4 Combination Therapy With DNMTi and/or HDACi and Other Anticancer Drugs

445

(1)

5 Epigenetic Therapy and Immune Response

446

(1)

6 Potential Applications in Precision Medicine

446

(1)

7 Challenges

446

(2)

8 Pharmacokinetic and Mechanic Challenges in Application of Epigenetic Drugs in Solid Tumors

448

(1)

9 Concluding Remarks

448

(5)

References

449

(4)

Chapter 22 Epigenetic Drug Discovery for Alzheimer's Disease

453

(46)

Ramon Cacabelos

Oscar Teijido

1 Introduction

454

(1)

2 Epigenetic Mechanisms of Alzheimer's Disease

455

(11)

2.1 DNA Methylation

455

(9)

2.2 Histone Modifications/Chromatin Remodeling

464

(1)

2.3 Noncoding RNAs

465

(1)

3 Epigenetic-Based Treatments for Alzheimer's Disease

466

(15)

3.1 DNA Methylation Activators

466

(1)

3.2 DNA Methylation Inhibitors

467

(5)

3.3 Histone Deacetylase Inhibitors

472

(3)

3.4 Sirtuin Inhibitors

475

(2)

3.5 Sirtuin Activators

477

(2)

3.6 Histone Acetyltransferase Modulators

479

(1)

3.7 Histone Methyltransferase and Demethylase Inhibitors

479

(1)

3.8 RNA Interference

480

(1)

3.9 Other Potential Epigenetic Treatments

481

(1)

4 Epigenetic Response to Drugs and Drug Resistance (Pharmacoepigenetics)

481

(1)

5 Conclusions and Future Directions

482

(17)

References

483

(16)

SECTION 5 CONCLUSIONS AND PERSPECTIVES

Chapter 23 Epigenetics of Aging and Longevity: Challenges and Future Directions

499

(12)

Axel Schumacher

1 Why We Age---An Introduction From the Epigenetics Perspective

499

(1)

2 Epigenetics and Precision Medicine

500

(2)

3 Applying Artificial Intelligence in Epigenetics Research

502

(2)

4 Epigenetics in Longitudinal N-of-1 Trials

504

(1)

5 Epigenetics and Blockchain Technology

505

(1)

6 Building an Epigenetic-Based Health Ecosystem

506

(1)

7 The Future of Epigenetics and Precision Health

507

(4)

References

508

(3)

Index

511

Dr. Alexey Moskalev earned his PhD from Moscow State University, Moscow, Russia in 2001. Since that time, Dr. Moskalevs research has focused on the genetics of longevity and aging, with emphasis on epigenetic regulation of aging, longevity, and stress resistance in animal models. He was a key contributor towards creating a database of biomarkers of aging in the Digital Ageing Atlas (DAA), and his lab has been supported by grants from the Russian Basic Research Foundation, the Presidium of the Russian Academy of Sciences, and the President of the Russian Federation through a program that funds leading young scientists. Currently, Dr. Moskalev is Vice-President of the Syktyvkar Branch of Russian Gerontology Society; President of the Komi branch of the Vavilov Society of Geneticists and Breeders; and a member of the editorial boards of Aging, Biogerontology, Frontiers in Genetics of Aging, Aging and Disease, Genes & Cells, and the SM Journal of Food and Nutritional Disorders. Additionally, he is Co-chair of the International Symposiums Genetics of Aging and Longevity” and Biomedical Innovation For Healthy Longevity”. Dr. Moskalev has published more than eighty scientific papers in peer reviewed journals on topics related to the genetics of aging and longevity, as well as DNR repair and defense genes in animal models. Dr. Vaiserman is head of the Laboratory of Epigenetics at the Institute of Gerontology, where his research has focused on long-term health consequences of adverse conditions in early life, genetic and epigenetic mechanisms of age-associated diseases, telomere length in patients with age-related chronic diseases, and molecular mechanisms mediating lifespan in Drosophila. He earned his PhD from the Institute of Gerontology, Kiev, Ukraine in 2004. During the last 7 years, Dr. Vaiserman was Project Leader for several Ukrainian government sponsored research projects. Dr. Vaiserman is also a member of the editorial boards of the journals Biogerontology, Frontiers in Genetics of Aging, and Gerontology & Geriatric Research. To-date, he has published four book chapters, as well as 65 papers in peer reviewed journals.

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