Handbook of the Biology of Aging, Eighth Edition, provides readers with an update on the rapid progress in the research of aging. It is a comprehensive synthesis and review of the latest and most important advances and themes in modern biogerontology, and focuses on the trend of 'big data' approaches in the biological sciences, presenting new strategies to analyze, interpret, and understand the enormous amounts of information being generated through DNA sequencing, transcriptomic, proteomic, and the metabolomics methodologies applied to aging related problems. The book includes discussions on longevity pathways and interventions that modulate aging, innovative new tools that facilitate systems-level approaches to aging research, the mTOR pathway and its importance in age-related phenotypes, new strategies to pharmacologically modulate the mTOR pathway to delay aging, the importance of sirtuins and the hypoxic response in aging, and how various pathways interact within the context of aging as a complex genetic trait, amongst others. - Covers the key areas in biological gerontology research in one volume, with an 80% update from the previous edition- Edited by Matt Kaeberlein and George Martin, highly respected voices and researchers within the biology of aging discipline- Assists basic researchers in keeping abreast of research and clinical findings outside their subdiscipline- Presents information that will help medical, behavioral, and social gerontologists in understanding what basic scientists and clinicians are discovering- New chapters on genetics, evolutionary biology, bone aging, and epigenetic control- Provides a close examination of the diverse research being conducted today in the study of the biology of aging, detailing recent breakthroughs and potential new directions
Front Cover 1
Handbook of the Biology of Aging 4
Copyright Page 5
Contents 6
Foreword 10
Preface 12
About the Editors 14
List of Contributors 16
I. Basic Mechanisms of Aging: Models and Systems 18
1 Longevity as a Complex Genetic Trait 20
Introduction 21
Defining the Aging Gene-Space 21
Direct Screens for Genetic Longevity Determinants 22
RNAi Screens in Nematodes 22
Knockout Screens in Budding Yeast 25
Overexpression Screens in Fruit Flies 26
Leveraging Genetic Diversity to Identify Aging Loci 27
Mapping Longevity Genes in Human Populations 27
Mapping Longevity Genes in Mouse Populations 33
Mouse–Human Concordance 36
Age-Associated Gene Expression Studies 36
Non-Genetic Sources of Complexity 38
Tissue-Specific Aging 38
Tissue-Specific Age-Related DNA Methylation 38
Telomere Shortening and Telomerase 39
Tissue-Specific Responses of Aging Pathways 40
Gene–Environment Interaction 41
Genetic Response to DR 41
DR: Quantity, Composition, and Timing 43
Environmental Temperature 45
Environmental Oxygen and the Hypoxic Response 46
Other Environmental Factors That Influence Aging 47
Emerging Tools for Studying Aging as a Complex Genetic Trait 48
High-Throughput Lifespan Assays in Yeast and Worms 48
Genome-Scale Mouse Knockout Collection 51
Collaborative Cross and Diversity Outbred Mice 51
Expression QTLs 56
Aging Biomarkers 57
Conclusions 59
References 60
2 The mTOR Pathway and Aging 72
Introduction 72
mTOR Signaling Pathway 73
Molecular Composition of mTOR Complex 73
Upstream Regulators of mTOR Complexes 73
Substrates and Actions of mTORC1 75
Substrates and Actions of mTORC2 76
Genetic Modulation of Longevity by TOR Signaling in Model Organisms 76
Rapamycin 79
Rapalogs 80
Potential Mechanisms of Life Span Extension by mTOR Inhibition 83
Translation 83
Autophagy 84
Anticancer Effect 84
Stem Cell Maintenance 84
mTOR in Age-Related Diseases 84
Cancer 84
Metabolic Disease 86
Cardiovascular 87
Neurodegeneration and Cognitive Decline 88
Immune Response 90
Conclusion 90
References 91
3 Sirtuins, Healthspan, and Longevity in Mammals 100
Introduction 101
Sirtuin-Driven Lifespan Extension in Invertebrates 101
Sirtuin Enzymatic Activity 103
Sirtuins and Mammalian Longevity 107
SIRT1 107
SIRT2 109
SIRT6 109
Genetic Variation of Human Sirtuins 111
SIRT1 111
SIRT3 112
Sirtuins as Modulators of Responses to CR 113
SIRT1 114
SIRT2 114
SIRT3 115
SIRT4 115
SIRT5 115
SIRT6 116
Roles for Sirtuins in Diverse Disease States 116
Cancer 116
SIRT1 116
SIRT2 118
SIRT3 118
SIRT4 119
SIRT6 120
SIRT7 121
Metabolic Syndrome 121
SIRT1 121
SIRT2 123
SIRT3 123
SIRT4 124
SIRT5 124
SIRT6 125
SIRT7 126
Cardiovascular Dysfunction 127
SIRT1 127
Other Sirtuins 128
Inflammatory Signaling 129
Neurodegenerative Disease 130
SIRT1 130
SIRT2 131
SIRT3 132
Sirtuin-Activating Compounds 132
Conclusion 134
Acknowledgments 136
References 137
4 The Hypoxic Response and Aging 150
Introduction 150
The Hypoxic Response 151
Signal Transduction Pathway 151
Hypoxic Signaling in Disease 155
VHL Disease 155
Cancer 156
Environmental Modifiers 156
Physiological Roles for the Hypoxic Response 159
Hypoxia 159
Development/Stem Cell Maintenance 159
Immunity 159
A Direct Role for the Hypoxic Response in Aging 160
The Hypoxic Response in Aging of Other Non-Mammalian Organisms 162
Interactions with Other Longevity Pathways 163
Sirtuins 163
Long-Lived Mitochondrial Mutants 164
Target of Rapamycin 165
HIF in Mammalian Aging 165
Positive Effects of Hypoxia 167
Conclusion 168
Acknowledgments 168
References 168
5 The Role of Neurosensory Systems in the Modulation of Aging 178
Introduction 178
Peripheral Systems of Sensory Perception 179
Environmental Sensing and the Regulation of Aging 180
Mechanisms of Sensory-Mediated Lifespan Regulation 182
The Next Steps in Mapping Sensory-Mediated Lifespan Circuits 186
Synthesis and Perspectives 188
References 191
6 The Naked Mole-Rat: A Resilient Rodent Model of Aging, Longevity, and Healthspan 196
What Is a Naked Mole-Rat? 198
Ecophysiology and Tolerance to Hypoxia 199
Eusociality 201
Successful Aging 202
Naked Mole-Rat Aging Biology 202
The Aging Brain 202
The Aging Heart 203
Aging Reproductive Profile 203
End of Life Pathology 203
Resistance to Toxins 204
Cancer Resistance in the Naked-Mole Rat 206
Maintenance of Genomic and Proteomic Integrity 208
Mechanisms in Successful Aging 208
Insulin mTOR Signaling 209
Oxidative Stress 210
Proteolytic Degradation Pathways Include Autophagy and UPS 213
Cytoprotective Signaling—Nrf2 Activity 214
Summary 215
References 216
7 Contributions of Telomere Biology to Human Age-Related Disease 222
Introduction 223
Telomere Structure and Function 223
Telomerase Structure, Function, and Regulation 225
Cellular Consequences of Telomere Dysfunction 227
Age-Related Changes in Telomere Length 229
Connections Between Human Age-Related Disease and Telomeres 231
Overall Longevity 233
Cardiovascular Diseases 233
Reproductive Aging 235
Type 2 Diabetes Mellitus 235
Osteoporosis 236
Idiopathic Pulmonary Fibrosis 236
Environmental Exposures 237
Cirrhosis 237
Cancer 238
Centenarians 240
Human Progeroid Disorders 241
p16 and Aging 243
Mouse Models 244
Pathologies Associated with Long Telomeres 245
Prospects for Prognostication and Intervention 246
Acknowledgments 247
References 247
8 Systems Approaches to Understanding Aging 258
Introduction 259
Transcriptomic Approaches Toward Understanding Aging 260
Gene Expression Profiles Related to Aging 260
Inferring Aging Regulators from Gene Expression Profiles 261
Regulatory Networks of Aging 262
MicroRNA, Systems Biology, and Aging 264
Knockdown or Knockout of miRNA Machinery 264
Finding Aging-Related miRNAs by High-Throughput Technologies 265
Searching for miRNA Targets In Silico and In Vivo 265
miRNA as Aging Biomarkers 267
Epigenomics and Aging 267
DNA Methylation and Aging 267
Histone Modification and Aging 269
Approaches to Detecting the Crosstalk of Epigenomic Markers 271
Integrated Microfluidic Systems for Studying Aging 271
Microfluidic Devices for Yeast Aging Study 272
Microfluidic Devices for C. elegans Aging Study 273
Conclusions 274
Acknowledgments 274
References 274
9 Integrative Genomics of Aging 280
Introduction 280
Post-Genome Technologies and Biogerontology 281
Genome-Wide Approaches and the Genetics of Aging and Longevity 281
Surveying the Aging Phenotype on a Grand Scale 284
Challenges in Data Analysis 287
Data Integration 288
Data and Databases 288
Finding Needles in Haystacks: Network Approaches and Multi-Dimensional Data Integration 289
Construction of Longevity Networks 290
Topological Features 291
Network Modularity 293
Multi-Dimensional Data Integration 293
Predictive Methods and Models 295
Concluding Remarks 296
Acknowledgments 297
References 297
10 NIA Interventions Testing Program: A Collaborative Approach for Investigating Interventions to Promote Healthy Aging 304
Introduction 305
Features of the ITP Experimental Design 305
Types of Intervention Proposals Sought by the ITP 308
Challenges Encountered Implementing Testing Protocols 309
Summary of ITP Findings 310
Stage II Studies 314
The ITP at 10 Years: Synopsis and Future Goals 316
References 319
11 Comparative Biology of Aging: Insights from Long-Lived Rodent Species 322
Introduction 322
Rodents as Models for Comparative Research 324
Cross-Species Biological Comparisons 326
Telomerase Maintenance and Replicative Senescence 327
Mechanisms for Controlling Cell Proliferation 327
Body Mass and Lifespan Shape Tumor Suppressor Mechanisms 328
Lifespan and Genome Stability 328
NMRs and BMRs 329
Hyaluronan Mediates Cancer Resistance in the NMR 330
Accurate Protein Synthesis in the NMR 331
Interferon Mediates Cancer Resistance in the BMR 332
Hyaluronan Evolved in Long-Lived Subterranean Rodents 333
Comparative Genomics of Aging and Cancer 333
Strategies for Comparative Genomics 333
Genomics of the NMR 334
Genomics of the BMR 335
Independent Adaptations to Subterranean Life 335
Comparative Genomics of Rodents and Other Mammals 335
Conclusion 336
References 338
II. The Pathobiology of Human Aging 342
12 Genetics of Human Aging 344
Introduction 344
Genetic Variation in Aging 345
Phenotypes of Human Aging 346
Experimental Models for Studying Human Aging 348
Study Designs for Discovering Genes Related to Human Aging 350
Genetic Linkage Analysis 352
Genetic Association Analysis 354
Genome-Wide Association Studies 355
Rare Variants in Aging 357
Candidate Studies in Aging 359
Functional Analysis 361
In Silico Analysis of Genetic Variants 362
Functional Analysis of Genetic Variants in In Vitro and In Vivo Models 366
Summary and Perspectives 369
References 370
13 The Aging Arterial Wall 376
Introduction 377
Proinflammatory Molecular Signature of the Aging Arterial Wall 378
Renin–Angiotensin System 378
Aldosterone and Mineralocorticoid Receptor-Mediated Signaling 378
Endothelin-1 Signaling 378
Adrenergic Receptor Signaling 379
Monocyte Chemoattractant Protein-1 380
Transforming Growth Factor-?1 380
Bone Morphogenetic Proteins 380
Platelet-Derived Growth Factor 380
Interleukin-6 and Tissue Necrosis Factor-Alpha 381
Matrix Metalloproteinases 381
Calpain-1/Calpastatin 381
Milk Fat Globule EGF-8 and Integrins 382
Vascular Cell Adhesion Molecule-1 and Intercellular Adhesion Molecule-1 382
Reactive Oxygen Species 382
Nitric Oxygen and Bioavailability 382
Cell Cycle Promoter Molecules 383
Intracellular Matrix Messenger Molecules, SMADs 383
Cell Cycle Inhibitory Molecules 383
Proinflammation Transcription Factors Ets-1 and NF-?B 384
Anti-Inflammatory Factors Nrf2, PPAR?, SIRT1, and FOXO3 384
Proliferation Transcription Factor AP-1 384
Macroscopic Age-Associated Altered Arterial CELL Phenotypes 385
Arterial Cellular Phenotypes 385
Endothelial Cells 385
EC Morphology and Junctions 385
EC Stiffening 385
EC Apoptosis 385
EC Senescence 385
EC Impairment 386
Vascular Smooth Muscle Cells 386
VSMC Proliferation 386
VSMC Senescence 387
VSMC Migration/Invasion 387
ECM Secretion 388
VSMC Stiffening 388
Fibroblasts 388
Arterial Wall Phenotypes 388
Endothelial Barrier Dysfunction 388
Prothrombosis 389
Fibrosis 389
Calcification 389
Elastin Fragmentation 389
Amyloidosis 390
Glycoxidization 390
Arterial Tissue Senescence 390
Clinical Signs of Arterial Wall Aging 391
Blood Pressure 391
Intimal-Medial Thickness 391
Pulse Wave Velocity 392
Endothelial Dysfunction 393
Interaction of Aging, Hypertension, and Atherosclerosis 393
Hypertension and Aging 393
Atherosclerosis and Aging 393
Interventions on Arterial Wall Aging 396
Blockade of Ang II Signaling, Adverse Remodeling, and Proinflammation 396
MMP Inhibition, Elastin Fragmentation, and ECM Deposition 396
Breakers of AGEs, RAGE and arterial stiffening 397
Caloric Restriction, Resveratrol, and Adverse Remodeling 397
Physical Conditioning and Proinflammation 397
Concluding Remarks and Future Perspectives 397
Acknowledgments 398
References 398
14 Age-Related Alterations in Neural Plasticity 408
Introduction 408
Short (Milliseconds) Timeframe: Paired-Pulse Facilitation and Paired-Pulse Depression 410
Intermediate (Seconds) Timeframe: Frequency Facilitation (FF) and the Post-Burst Afterhyperpolarization 412
Frequency Facilitation 412
Post-Burst Afterhyperpolarization 413
Long (Minutes to Days) Timeframe: Long-Term Potentiation and Long-Term Depression 415
Neural Plasticity and the Calcium Dysregulation Hypothesis of Aging 418
References 419
15 The Aging Immune System: Dysregulation, Compensatory Mechanisms, and Prospects for Intervention 424
Introduction 425
Innate and Adaptive Immunity 425
Age and Immunity 427
Effect of Age on Hematopoiesis 428
Effect of Age on Innate Immunity 431
NK Cells 431
Dendritic Cells 432
Effect of Age on Adaptive Immunity 432
Impact of Thymic Involution and Thymectomy on T Cells 433
Immune Cell Function 436
T-Cell Function 436
B-Cell Function 437
Clinical Consequences of Immunosenescence 437
Effect of Age on Vaccination 438
Immune Senescence and All-Cause Mortality 440
Interventions to Restore Appropriate Immunity 441
Perspectives 443
References 444
16 Vascular Disease in Hutchinson Gilford Progeria Syndrome and Aging: Common Phenotypes and Potential Mechanisms 450
Introduction 451
Progeria as a Model for Studying Vascular Disease 451
Vascular Pathology in Progeria and Aging 451
Hypertension 452
Adventitial Fibrosis 452
Medial Cell Death 454
Atherosclerosis in Progeria and Aging 455
ECM Changes in Progeria and Aging and Their Potential Contribution to Atherosclerosis 457
Potential Molecular Mechanisms Driving Vascular Disease in Progeria 460
A-Type Lamin Mutation and Progerin Processing 460
Progerin Expression in Normal Aging Vasculature 461
Chromatin Reorganization 462
Altered Transcription Factor Regulation 462
DNA Damage and Dysfunctional Telomeres 463
Mechanosensitivity 463
Dysfunctional Stem Cell Niche 464
Mouse Models of Progeria 465
Current Status of Clinical Intervention Trials for Progeria 465
Concluding Remarks 467
References 468
17 Cardiac Aging 476
Introduction 477
Cardiac Aging in Humans 477
Murine Model of Cardiac Aging 480
Molecular Mechanisms of Cardiac Aging 482
Role of Mitochondria and ROS in Cardiac Aging 482
Nutrient Signaling in Cardiac Aging 483
Neurohormonal Regulation of Cardiac Aging 485
Renin–Angiotensin–Aldosterone System (RAAS) 485
Adrenergic Signaling 485
Insulin/IGF-1 Signaling 486
Aging of Cardiac Stem/Progenitor Cells 486
Decreased Cardiac Functional Reserve in Aging 487
Mechanisms of Progression to Heart Failure in Old Age 488
Mitochondrial Dysfunction and Abnormalities in Energetics 488
Increased Cardiomyocyte Death and ECM Remodeling 490
Alteration of Calcium Handling Proteins 491
Hypoxic Response and Angiogenesis 492
Other Models of Cardiac Aging 492
Drosophila: An Invertebrate Model of Cardiac Senescence 492
Normal Aging of the Drosophila Heart 492
Heart Rate 492
Rhythmicity 493
Fiber Structure 493
Stress Resistance 493
Genetic Regulation 493
Ion Channels 494
Contractile Proteins 494
ROS-Scavenging Proteins 495
Nutrient-Sensing Signaling Pathways 495
Exercise 496
Large Animal Models of Cardiac Aging 496
Interventions to Delay or Reverse Vertebrate Cardiac Aging 497
Calorie Restriction and Its Mimetics 497
Mitochondrial Intervention 498
Antioxidants 498
SS-31 499
Inhibition of Renin–Angiotensin–Aldosterone signaling 500
Other Novel Agents 500
References 501
18 Current Status of Research on Trends in Morbidity, Healthy Life Expectancy, and the Compression of Morbidity 512
Introduction 512
Dimensions of Morbidity 513
The Length of Life Cycles and Population Health 514
Trends in Population Prevalence of Physiological Dysregulation, Diseases and Conditions, Functioning Loss and Disability, a ... 514
Length of Life and Length of Healthy Life 517
Conclusions 521
References 521
19 On the Compression of Morbidity: From 1980 to 2015 and Beyond 524
Introduction 524
Compression of Morbidity 524
The Science of Postponement of Disability 526
Synonyms and Antonyms 526
Human Aging 528
Themes and Paradigms 528
Longitudinal Study of Human Aging 528
Long-Distance Runners Versus Community Controls 531
Two or More Risk Factors (Smoking, Inactivity, or Obesity) Versus None of These 533
Morbidity is Best Compressed by Regular, Vigorous, and Sustained Exercise 535
Disease, Diagnosis, Morbidities, and Trajectories 536
Delayed Aging 537
Concluding Remarks 538
State of the Evidence 538
Possibilities and Uncertainties 539
References 539
Author Index 542
Subject Index 560
List of Contributors
Rolf Bodmer, Development, Aging, and Regeneration Program Sanford-Burnham Medical Research Institute, La Jolla, CA, USA
Rochelle Buffenstein
Barshop Institute for Aging and Longevity Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Hao Cheng, Chinese Academy of Sciences Key Laboratory of Computational Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
Ying-Ann Chiao, Department of Pathology, University of Washington, Seattle, WA, USA
Miook Cho, Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA
Eileen M. Crimmins, Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA
Dao-Fu Dai, Department of Pathology, University of Washington, Seattle, WA, USA
João Pedro de Magalhães, Integrative Genomics of Ageing Group, Institute of Integrative Biology, University of Liverpool, Liverpool, UK
James F. Fries, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
William Giblin, Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA
Vera Gorbunova, Department of Biology, University of Rochester, Rochester, NY, USA
Jing-Dong J Han, Chinese Academy of Sciences Key Laboratory of Computational Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
David E. Harrison, The Jackson Laboratory, Bar Harbor, ME, USA
Ingrid A. Harten
Matrexa LLC, Seattle, WA, USA
Matrix Biology Program, Benaroya Research Institute at Virginia Mason, Seattle, WA, USA
Lei Hou, Chinese Academy of Sciences Key Laboratory of Computational Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
F. Brad Johnson, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Matt R. Kaeberlein, Department of Pathology, University of Washington, Seattle, WA, USA
Brian K. Kennedy, The Buck Institute for Research on Aging, Novato, CA, USA
Ron Korstanje, The Jackson Laboratory, Bar Harbor, ME, USA
Edward G. Lakatta, Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Biomedical Research Center, Baltimore, MD, USA
Scott F. Leiser, Department of Pathology, University of Washington, Seattle, WA, USA
Morgan E. Levine, University of California Los Angeles, Los Angeles, CA, USA
Kaitlyn N. Lewis
Barshop Institute for Aging and Longevity Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
David B. Lombard
Department of Pathology, University of Michigan, Ann Arbor, MI, USA
Institute of Gerontology, University of Michigan, Ann Arbor, MI, USA
Hillary A. Miller, Department of Pathology, University of Washington, Seattle, WA, USA
Richard A. Miller, Department of Pathology and Geriatrics Center, University of Michigan, Ann Arbor, MI, USA
Robert E. Monticone, Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Biomedical Research Center, Baltimore, MD, USA
Shannon J. Moore, Molecular and Behavioral Neuroscience Institute, University of Michigan Medical School, Ann Arbor, MI, USA
Ludmila Müller, Max Planck Institute for Human Development, Berlin, Germany
Geoffrey G. Murphy
Molecular and Behavioral Neuroscience Institute, University of Michigan Medical School, Ann Arbor, MI, USA
Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA
Nancy L. Nadon, Division of Aging Biology, National Institute on Aging, Bethesda, MD, USA
Monique N. O’Leary, The Buck Institute for Research on Aging, Novato, CA, USA
Michelle Olive, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
Graham Pawelec, Center for Medical Research, University of Tübingen, Tübingen, Germany
Scott D. Pletcher
Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI, USA
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA
Geriatrics Center, University of Michigan, Ann Arbor, MI, USA
Peter S. Rabinovitch, Department of Pathology, University of Washington, Seattle, WA, USA
Katherine H. Schreiber, The Buck Institute for Research on Aging, Novato, CA, USA
Andrei Seluanov, Department of Biology, University of Rochester, Rochester, NY, USA
Shufei Song
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Biochemistry and Molecular Biophysics Graduate Group, University of Pennsylvania, Philadelphia, PA, USA
Randy Strong, Department of Pharmacology, The University of Texas Health Science Center at San Antonio, and the Geriatric Research, Education and Clinical Center and Research Service of the South Texas Veterans Health Care System, San Antonio, TX, USA
Yousin Suh
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA
George L. Sutphin, The Jackson Laboratory, Bar Harbor, ME, USA
Hazel H. Szeto, Department of Pharmacology, Joan and Sanford I Weill Medical College of Cornell University, New York, NY, USA
Robi Tacutu, Integrative Genomics of Ageing Group, Institute of Integrative Biology, University of Liverpool, Liverpool, UK
Michael Van Meter, Department of Biology, University of Rochester, Rochester, NY, USA
Dan Wang, Chinese Academy of Sciences Key Laboratory of Computational Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
Mingyi Wang, Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Biomedical Research Center, Baltimore, MD, USA
Michael J. Waterson, Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI, USA
Robert J. Wessells, Geriatrics Center and Institute of Gerontology, University of Michigan, Ann Arbor, MI, USA
Thomas N. Wight
Matrexa LLC, Seattle, WA,...
| Erscheint lt. Verlag | 20.8.2015 |
|---|---|
| Sprache | englisch |
| Themenwelt | Geisteswissenschaften ► Psychologie ► Allgemeine Psychologie |
| Geisteswissenschaften ► Psychologie ► Entwicklungspsychologie | |
| Medizin / Pharmazie ► Medizinische Fachgebiete ► Geriatrie | |
| Naturwissenschaften ► Biologie ► Genetik / Molekularbiologie | |
| ISBN-10 | 0-12-411620-5 / 0124116205 |
| ISBN-13 | 978-0-12-411620-7 / 9780124116207 |
| Haben Sie eine Frage zum Produkt? |
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