Handbook of the Biology of Aging
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.
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