Handbook of the Biology of Aging

Editors: Masoro, Edward J. and Austad, Steven N.
Publication Year: 2016
Publisher: Elsevier Science & Technology

Single-User Purchase Price: $119.94
Unlimited-User Purchase Price: $179.91
ISBN: 978-0-12-411596-5
Category: Science - Biology
Image Count: 80
Book Status: Available
Table of Contents

The eighth edition of this very successful handbook on how basic aging processes and medical physiology affect biological systems includes new discussions of a variety of topics, including longevity pathways and interventions that modulate aging, innovative new tools that facilitate systems-level approaches to aging research and more.

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Table of Contents

  • Foreword
  • Preface
  • About the Editors
  • List of Contributors
  • Part I Basic Mechanisms of Aging: Models and Systems
  • 1. Longevity as a Complex Genetic Trait
  • Introduction
  • Defining the Aging Gene-Space
  • Direct Screens for Genetic Longevity Determinants
  • RNAi Screens in Nematodes
  • Knockout Screens in Budding Yeast
  • Overexpression Screens in Fruit Flies
  • Leveraging Genetic Diversity to Identify Aging Loci
  • Mapping Longevity Genes in Human Populations
  • Mapping Longevity Genes in Mouse Populations
  • Mouse–Human Concordance
  • Age-Associated Gene Expression Studies
  • Non-Genetic Sources of Complexity
  • Tissue-Specific Aging
  • Tissue-Specific Age-Related DNA Methylation
  • Telomere Shortening and Telomerase
  • Tissue-Specific Responses of Aging Pathways
  • Gene–Environment Interaction
  • Genetic Response to DR
  • DR: Quantity, Composition, and Timing
  • Environmental Temperature
  • Environmental Oxygen and the Hypoxic Response
  • Other Environmental Factors That Influence Aging
  • Emerging Tools for Studying Aging as a Complex Genetic Trait
  • High-Throughput Lifespan Assays in Yeast and Worms
  • Genome-Scale Mouse Knockout Collection
  • Collaborative Cross and Diversity Outbred Mice
  • Expression QTLs
  • Aging Biomarkers
  • Conclusions
  • References
  • 2. The mTOR Pathway and Aging
  • Introduction
  • mTOR Signaling Pathway
  • Molecular Composition of mTOR Complex
  • Upstream Regulators of mTOR Complexes
  • Substrates and Actions of mTORC1
  • Substrates and Actions of mTORC2
  • Genetic Modulation of Longevity by TOR Signaling in Model Organisms
  • Rapamycin
  • Rapalogs
  • Potential Mechanisms of Life Span Extension by mTOR Inhibition
  • Translation
  • Autophagy
  • Anticancer Effect
  • Stem Cell Maintenance
  • mTOR in Age-Related Diseases
  • Cancer
  • Metabolic Disease
  • Cardiovascular
  • Neurodegeneration and Cognitive Decline
  • Immune Response
  • Conclusion
  • References
  • 3. Sirtuins, Healthspan, and Longevity in Mammals
  • Introduction
  • Sirtuin-Driven Lifespan Extension in Invertebrates
  • Sirtuin Enzymatic Activity
  • Sirtuins and Mammalian Longevity
  • SIRT1
  • SIRT2
  • SIRT6
  • Genetic Variation of Human Sirtuins
  • SIRT1
  • SIRT3
  • Sirtuins as Modulators of Responses to CR
  • SIRT1
  • SIRT2
  • SIRT3
  • SIRT4
  • SIRT5
  • SIRT6
  • Roles for Sirtuins in Diverse Disease States
  • Cancer
  • SIRT1
  • SIRT2
  • SIRT3
  • SIRT4
  • SIRT6
  • SIRT7
  • Metabolic Syndrome
  • SIRT1
  • SIRT2
  • SIRT3
  • SIRT4
  • SIRT5
  • SIRT6
  • SIRT7
  • Cardiovascular Dysfunction
  • SIRT1
  • Other Sirtuins
  • Inflammatory Signaling
  • Neurodegenerative Disease
  • SIRT1
  • SIRT2
  • SIRT3
  • Sirtuin-Activating Compounds
  • Conclusion
  • Acknowledgments
  • References
  • 4. The Hypoxic Response and Aging
  • Introduction
  • The Hypoxic Response
  • Signal Transduction Pathway
  • Hypoxic Signaling in Disease
  • VHL Disease
  • Cancer
  • Environmental Modifiers
  • Physiological Roles for the Hypoxic Response
  • Hypoxia
  • Development/Stem Cell Maintenance
  • Immunity
  • A Direct Role for the Hypoxic Response in Aging
  • The Hypoxic Response in Aging of Other Non-Mammalian Organisms
  • Interactions with Other Longevity Pathways
  • Sirtuins
  • Long-Lived Mitochondrial Mutants
  • Target of Rapamycin
  • HIF in Mammalian Aging
  • Positive Effects of Hypoxia
  • Conclusion
  • Acknowledgments
  • References
  • 5. The Role of Neurosensory Systems in the Modulation of Aging
  • Introduction
  • Peripheral Systems of Sensory Perception
  • Environmental Sensing and the Regulation of Aging
  • Mechanisms of Sensory-Mediated Lifespan Regulation
  • The Next Steps in Mapping Sensory-Mediated Lifespan Circuits
  • Synthesis and Perspectives
  • References
  • 6. The Naked Mole-Rat: A Resilient Rodent Model of Aging, Longevity, and Healthspan
  • What Is a Naked Mole-Rat?
  • Ecophysiology and Tolerance to Hypoxia
  • Eusociality
  • Successful Aging
  • Naked Mole-Rat Aging Biology
  • The Aging Brain
  • The Aging Heart
  • Aging Reproductive Profile
  • End of Life Pathology
  • Resistance to Toxins
  • Cancer Resistance in the Naked-Mole Rat
  • Maintenance of Genomic and Proteomic Integrity
  • Mechanisms in Successful Aging
  • Insulin mTOR Signaling
  • Oxidative Stress
  • Proteolytic Degradation Pathways Include Autophagy and UPS
  • Cytoprotective Signaling—Nrf2 Activity
  • Summary
  • References
  • 7. Contributions of Telomere Biology to Human Age-Related Disease
  • Introduction
  • Telomere Structure and Function
  • Telomerase Structure, Function, and Regulation
  • Cellular Consequences of Telomere Dysfunction
  • Age-Related Changes in Telomere Length
  • Connections Between Human Age-Related Disease and Telomeres
  • Overall Longevity
  • Cardiovascular Diseases
  • Reproductive Aging
  • Type 2 Diabetes Mellitus
  • Osteoporosis
  • Idiopathic Pulmonary Fibrosis
  • Environmental Exposures
  • Cirrhosis
  • Cancer
  • Centenarians
  • Human Progeroid Disorders
  • p16 and Aging
  • Mouse Models
  • Pathologies Associated with Long Telomeres
  • Prospects for Prognostication and Intervention
  • Acknowledgments
  • References
  • 8. Systems Approaches to Understanding Aging
  • Introduction
  • Transcriptomic Approaches Toward Understanding Aging
  • Gene Expression Profiles Related to Aging
  • Inferring Aging Regulators from Gene Expression Profiles
  • Regulatory Networks of Aging
  • MicroRNA, Systems Biology, and Aging
  • Knockdown or Knockout of miRNA Machinery
  • Finding Aging-Related miRNAs by High-Throughput Technologies
  • Searching for miRNA Targets In Silico and In Vivo
  • miRNA as Aging Biomarkers
  • Epigenomics and Aging
  • DNA Methylation and Aging
  • Histone Modification and Aging
  • Approaches to Detecting the Crosstalk of Epigenomic Markers
  • Integrated Microfluidic Systems for Studying Aging
  • Microfluidic Devices for Yeast Aging Study
  • Microfluidic Devices for C. elegans Aging Study
  • Conclusions
  • Acknowledgments
  • References
  • 9. Integrative Genomics of Aging
  • Introduction
  • Post-Genome Technologies and Biogerontology
  • Genome-Wide Approaches and the Genetics of Aging and Longevity
  • Surveying the Aging Phenotype on a Grand Scale
  • Challenges in Data Analysis
  • Data Integration
  • Data and Databases
  • Finding Needles in Haystacks: Network Approaches and Multi-Dimensional Data Integration
  • Construction of Longevity Networks
  • Topological Features
  • Network Modularity
  • Multi-Dimensional Data Integration
  • Predictive Methods and Models
  • Concluding Remarks
  • Acknowledgments
  • References
  • 10. NIA Interventions Testing Program: A Collaborative Approach for Investigating Interventions to Promote Healthy Aging
  • Introduction
  • Features of the ITP Experimental Design
  • Types of Intervention Proposals Sought by the ITP
  • Challenges Encountered Implementing Testing Protocols
  • Summary of ITP Findings
  • Stage II Studies
  • The ITP at 10 Years: Synopsis and Future Goals
  • References
  • 11. Comparative Biology of Aging: Insights from Long-Lived Rodent Species
  • Introduction
  • Rodents as Models for Comparative Research
  • Cross-Species Biological Comparisons
  • Telomerase Maintenance and Replicative Senescence
  • Mechanisms for Controlling Cell Proliferation
  • Body Mass and Lifespan Shape Tumor Suppressor Mechanisms
  • Lifespan and Genome Stability
  • NMRs and BMRs
  • Hyaluronan Mediates Cancer Resistance in the NMR
  • Accurate Protein Synthesis in the NMR
  • Interferon Mediates Cancer Resistance in the BMR
  • Hyaluronan Evolved in Long-Lived Subterranean Rodents
  • Comparative Genomics of Aging and Cancer
  • Strategies for Comparative Genomics
  • Genomics of the NMR
  • Genomics of the BMR
  • Independent Adaptations to Subterranean Life
  • Comparative Genomics of Rodents and Other Mammals
  • Conclusion
  • References
  • Part II The Pathobiology of Human Aging
  • 12. Genetics of Human Aging
  • Introduction
  • Genetic Variation in Aging
  • Phenotypes of Human Aging
  • Experimental Models for Studying Human Aging
  • Study Designs for Discovering Genes Related to Human Aging
  • Genetic Linkage Analysis
  • Genetic Association Analysis
  • Genome-Wide Association Studies
  • Rare Variants in Aging
  • Candidate Studies in Aging
  • Functional Analysis
  • In Silico Analysis of Genetic Variants
  • Functional Analysis of Genetic Variants in In Vitro and In Vivo Models
  • Summary and Perspectives
  • References
  • 13. The Aging Arterial Wall
  • Introduction
  • Proinflammatory Molecular Signature of the Aging Arterial Wall
  • Renin–Angiotensin System
  • Aldosterone and Mineralocorticoid Receptor-Mediated Signaling
  • Endothelin-1 Signaling
  • Adrenergic Receptor Signaling
  • Monocyte Chemoattractant Protein-1
  • Transforming Growth Factor-β1
  • Bone Morphogenetic Proteins
  • Platelet-Derived Growth Factor
  • Interleukin-6 and Tissue Necrosis Factor-Alpha
  • Matrix Metalloproteinases
  • Calpain-1/Calpastatin
  • Milk Fat Globule EGF-8 and Integrins
  • Vascular Cell Adhesion Molecule-1 and Intercellular Adhesion Molecule-1
  • Reactive Oxygen Species
  • Nitric Oxygen and Bioavailability
  • Cell Cycle Promoter Molecules
  • Intracellular Matrix Messenger Molecules, SMADs
  • Cell Cycle Inhibitory Molecules
  • Proinflammation Transcription Factors Ets-1 and NF-κB
  • Anti-Inflammatory Factors Nrf2, PPARγ, SIRT1, and FOXO3
  • Proliferation Transcription Factor AP-1
  • Macroscopic Age-Associated Altered Arterial Phenotypes
  • Arterial Cellular Phenotypes
  • Endothelial Cells
  • Vascular Smooth Muscle Cells
  • Fibroblasts
  • Arterial Wall Phenotypes
  • Endothelial Barrier Dysfunction
  • Prothrombosis
  • Fibrosis
  • Calcification
  • Elastin Fragmentation
  • Amyloidosis
  • Glycoxidization
  • Arterial Tissue Senescence
  • Clinical Signs of Arterial Wall Aging
  • Blood Pressure
  • Intimal-Medial Thickness
  • Pulse Wave Velocity
  • Endothelial Dysfunction
  • Interaction of Aging, Hypertension, and Atherosclerosis
  • Hypertension and Aging
  • Atherosclerosis and Aging
  • Interventions on Arterial Wall Aging
  • Blockade of Ang II Signaling, Adverse Remodeling, and Proinflammation
  • MMP Inhibition, Elastin Fragmentation, and ECM Deposition
  • Breakers of AGEs, RAGE and arterial stiffening
  • Caloric Restriction, Resveratrol, and Adverse Remodeling
  • Physical Conditioning and Proinflammation
  • Concluding Remarks and Future Perspectives
  • Acknowledgment
  • References
  • 14. Age-Related Alterations in Neural Plasticity
  • Introduction
  • Short (Milliseconds) Timeframe: Paired-Pulse Facilitation and Paired-Pulse Depression
  • Intermediate (Seconds) Timeframe: Frequency Facilitation (FF) and the Post-Burst Afterhyperpolarization
  • Frequency Facilitation
  • Post-Burst Afterhyperpolarization
  • Long (Minutes to Days) Timeframe: Long-Term Potentiation and Long-Term Depression
  • Neural Plasticity and the Calcium Dysregulation Hypothesis of Aging
  • References
  • 15. The Aging Immune System: Dysregulation, Compensatory Mechanisms, and Prospects for Intervention
  • Introduction
  • Innate and Adaptive Immunity
  • Age and Immunity
  • Effect of Age on Hematopoiesis
  • Effect of Age on Innate Immunity
  • NK Cells
  • Dendritic Cells
  • Effect of Age on Adaptive Immunity
  • Impact of Thymic Involution and Thymectomy on T Cells
  • Immune Cell Function
  • T-Cell Function
  • B-Cell Function
  • Clinical Consequences of Immunosenescence
  • Effect of Age on Vaccination
  • Immune Senescence and All-Cause Mortality
  • Interventions to Restore Appropriate Immunity
  • Perspectives
  • References
  • 16. Vascular Disease in Hutchinson Gilford Progeria Syndrome and Aging: Common Phenotypes and Potential Mechanisms
  • Introduction
  • Progeria as a Model for Studying Vascular Disease
  • Vascular Pathology in Progeria and Aging
  • Hypertension
  • Adventitial Fibrosis
  • Medial Cell Death
  • Atherosclerosis in Progeria and Aging
  • ECM Changes in Progeria and Aging and Their Potential Contribution to Atherosclerosis
  • Potential Molecular Mechanisms Driving Vascular Disease in Progeria
  • A-Type Lamin Mutation and Progerin Processing
  • Progerin Expression in Normal Aging Vasculature
  • Chromatin Reorganization
  • Altered Transcription Factor Regulation
  • DNA Damage and Dysfunctional Telomeres
  • Mechanosensitivity
  • Dysfunctional Stem Cell Niche
  • Mouse Models of Progeria
  • Current Status of Clinical Intervention Trials for Progeria
  • Concluding Remarks
  • References
  • 17. Cardiac Aging
  • Introduction
  • Cardiac Aging in Humans
  • Murine Model of Cardiac Aging
  • Molecular Mechanisms of Cardiac Aging
  • Role of Mitochondria and ROS in Cardiac Aging
  • Nutrient Signaling in Cardiac Aging
  • Neurohormonal Regulation of Cardiac Aging
  • Renin–Angiotensin–Aldosterone System (RAAS)
  • Adrenergic Signaling
  • Insulin/IGF-1 Signaling
  • Aging of Cardiac Stem/Progenitor Cells
  • Decreased Cardiac Functional Reserve in Aging
  • Mechanisms of Progression to Heart Failure in Old Age
  • Mitochondrial Dysfunction and Abnormalities in Energetics
  • Increased Cardiomyocyte Death and ECM Remodeling
  • Alteration of Calcium Handling Proteins
  • Hypoxic Response and Angiogenesis
  • Other Models of Cardiac Aging
  • Drosophila: An Invertebrate Model of Cardiac Senescence
  • Normal Aging of the Drosophila Heart
  • Genetic Regulation
  • Large Animal Models of Cardiac Aging
  • Interventions to Delay or Reverse Vertebrate Cardiac Aging
  • Calorie Restriction and Its Mimetics
  • Mitochondrial Intervention
  • Antioxidants
  • SS-31
  • Inhibition of Renin–Angiotensin–Aldosterone signaling
  • Other Novel Agents
  • References
  • 18. Current Status of Research on Trends in Morbidity, Healthy Life Expectancy, and the Compression of Morbidity
  • Introduction
  • Dimensions of Morbidity
  • The Length of Life Cycles and Population Health
  • Trends in Population Prevalence of Physiological Dysregulation, Diseases and Conditions, Functioning Loss and Disability, and Life Expectancy
  • Length of Life and Length of Healthy Life
  • Conclusions
  • References
  • 19. On the Compression of Morbidity: From 1980 to 2015 and Beyond
  • Introduction
  • Compression of Morbidity
  • The Science of Postponement of Disability
  • Synonyms and Antonyms
  • Human Aging
  • Themes and Paradigms
  • Longitudinal Study of Human Aging
  • Long-Distance Runners Versus Community Controls
  • Two or More Risk Factors (Smoking, Inactivity, or Obesity) Versus None of These
  • Morbidity is Best Compressed by Regular, Vigorous, and Sustained Exercise
  • Disease, Diagnosis, Morbidities, and Trajectories
  • Delayed Aging
  • Concluding Remarks
  • State of the Evidence
  • Possibilities and Uncertainties
  • References
  • Subject Index