دانلود کتاب Aging Mechanisms II: Longevity, Metabolism, and Brain Aging

فهرست مطالب :

Preface
Contents
Contributors
Part I: From Hypothesis to Mechanisms
Chapter 1: An Unsolved Problem in Gerontology Yet: Molecular Mechanisms of Biological Aging-A Historical and Critical Overview
1.1 Introduction
1.2 The Definition of Aging
1.3 Aging Theories
1.4 Mutation Theory of Aging/Genome Instability Theory of Aging
1.5 Free Radical Theory of Aging/Oxidative Stress Theory of Aging
1.6 The Mitochondrial Theory of Aging
1.7 The Error Catastrophe Theory of Aging
1.8 The Altered Protein Theory of Aging/Protein Homeostasis or Proteostasis Theory of Aging
1.9 Dysdifferentiation Theory of Aging/Epigenetic Theory of Aging
1.10 The Hyperfunction Theory of Aging
1.11 Summary and Perspectives
References
Part II: Human Longevity: Accelerated Aging and Centenarians
Chapter 2: Clinical and Basic Biology of Werner Syndrome, the Model Disease of Human Aging
2.1 Clinical Features and Pathogenesis of Werner Syndrome
2.1.1 Introduction
2.1.2 Diagnostic Criteria
2.1.3 Werner Syndrome Registry
2.1.3.1 General Information
Age at Onset and Diagnosis
Physique
Life Expectancy
Laboratory Test
2.1.3.2 Symptoms
Sarcopenia
Diabetes
Dyslipidemia
Fatty Liver
Atherosclerosis
Malignancy
Osteoporosis
Skin Ulcers
Infection
Calcification in Tendons
2.2 Basic Research and Molecular Mechanisms of Werner Syndrome
2.2.1 Werner Gene and Protein
2.2.2 WRN and DNA Damage Repair
2.2.3 WRN and Telomeres
2.2.4 WRN and Mitochondria, mTOR, and Autophagy
2.2.5 Phenotype of WRN KO Mice
2.2.6 WRN and Stem Cell Senescence and Epigenome Regulation
2.2.7 WS Patient-Derived iPS Cells
2.2.8 Malignancy and WRN
2.3 Conclusion
References
Chapter 3: Biomarkers of Healthy Longevity: Lessons from Supercentenarians in Japan
3.1 Introduction
3.2 Demography and Functional Status of Supercentenarians
3.3 Cardiovascular Biomarkers and Exceptional Survival
3.4 Adiponectin
3.5 Immunological Biomarkers of Healthy Longevity
3.6 Future Prospects
References
Part III: Cellular Aging and Lower Animal Models
Chapter 4: Cellular Aging and Metabolites in Aging
4.1 Introduction
4.2 Historical Theory and Replicative Senescence
4.3 Telomere-Dependent and Telomere-Independent Senescence
4.4 Double-Edged Sword of SIS
4.5 Senescence Markers
4.6 The Aging Hypothesis Relevant to Metabolic Profiles
4.7 Metabolomic Approach for Human Whole Blood
4.8 Blood Metabolites for Aging Markers
4.9 Blood Metabolites for Fasting Markers
4.10 Frailty Markers for Antioxidation, Cognition, and Mobility
4.11 Summary
References
Chapter 5: To G0 or Not to G0: Cell Cycle Paradox in Senescence and Brain Aging
5.1 Alzheimer´s Disease
5.2 Cellular Senescence
5.3 Cellular Senescence in Post-mitotic Cells
5.4 Proteostasis Failure as a Driver of Neuronal Senescence
5.5 Neuronal Senescence: Pleiotropic Response
5.6 Conclusion
References
Chapter 6: C. elegans Longevity Genes
6.1 Caenorhabditis elegans
6.2 Methodology
6.3 Aging Phenotype
6.4 Longevity Genes
References
Chapter 7: Understanding the Functions of Longevity Genes in Drosophila
7.1 Drosophila melanogaster as a Model System to Study Aging
7.1.1 Antioxidant
7.1.1.1 Cytoplasmic SOD (Sod1)
7.1.1.2 Mitochondrial SOD (Sod2)
7.1.1.3 Extracellular SOD (Sod3)
7.1.1.4 Catalase (Cat)
7.1.1.5 Thioredoxin (Trx-2, TrxT, dhd)
7.1.2 Insulin/IGF-1TOR Pathway
7.1.3 JNK Signaling Pathway
7.1.4 Epigenetic Mechanism
7.2 Epigenetic Inheritance of Longevity
References
Part IV: Metabolism: Factors Affecting Tissue Aging
Chapter 8: NAD+ Metabolism in Aging
8.1 Introduction
8.2 NAD+ Biosynthesis
8.3 NAD+ Consumption
8.4 NAD+ Levels Decline with Age
8.5 Effects of Age-Related NAD+ Decline on Hallmarks of Aging
8.6 Role of NAD+ in Age-Associated Functional Decline of Organs
8.6.1 Liver
8.6.2 Adipose Tissue
8.6.3 Skeletal Muscle
8.6.4 Kidney
8.7 NAD+ Precursors for Restoring NAD+ Levels in Animals and Humans
8.8 Conclusions
References
Chapter 9: Mitochondrial Dysfunction and Growth Differentiation Factor 15 in Aging
9.1 Introduction
9.2 GDF15 as a Marker for Mitochondrial Dysfunction and Mitochondrial Diseases
9.2.1 Cybrid Cells with Pathogenic mtDNA Mutations
9.2.2 Energy Metabolism in Cybrid Cells with Mitochondrial Dysfunction
9.2.3 Transcriptional Response to Impaired Energy Metabolism in Cybrid Cells
9.2.4 GDF15 as a Marker for Mitochondrial Dysfunction
9.2.5 GDF15 as a Biomarker for Mitochondrial Diseases
9.3 GDF15 and Aging
9.3.1 Characteristics of GDF15
9.3.2 GDF15 Functions Through Its Specific Receptor GFRAL
9.3.3 Correlation of Circulating GDF15 Levels with Age
9.3.4 GDF15 and Adverse Outcomes in Older Adults
9.3.5 GDF15 and Age-Related Diseases
9.4 Discussion and Perspectives
References
Chapter 10: Sirtuins and Metabolic Health
10.1 Introduction
10.2 Sirtuins in Oxidative Stress and Mitochondrial Biogenesis (Fig. 10.1)
10.3 Sirtuins in Inflammation (Fig. 10.1)
10.4 Sirtuins in Autophagy (Fig. 10.1)
10.5 Sirtuins in Apoptosis (Fig. 10.1)
10.6 Interventions Targeting Sirtuins
10.7 Perspectives
References
Chapter 11: Autophagy in Aging and Longevity
11.1 Overview of Autophagy
11.2 Activation of Autophagy Is One of the Convergent Mechanisms of Animal Longevity
11.3 Autophagic Activity Declines with Age
11.4 Autophagy and Age-Related Neurodegenerative Diseases
11.5 Molecular Mechanism Regulating Autophagy and Longevity
11.6 Intervention of Aging via Modulating Autophagy
11.7 Conclusion
References
Chapter 12: Sarcopenia: Current Topics and Future Perspective
12.1 What Is Sarcopenia?
12.2 How to Diagnose Sarcopenia
12.3 AWGS 2019
12.4 Utilization of Phase Angle
12.5 Prevalence of Sarcopenia
12.6 Etiology of Sarcopenia
12.7 Genetics of Sarcopenia
12.8 Prognosis of Sarcopenia
12.9 Relationship Between Sarcopenia and Disease
12.10 Macroscopic Features of Age-Related Changes in Skeletal Muscle
12.11 Microscopic Features of Age-Related Changes in Skeletal Muscle
12.12 Prevention of Sarcopenia
12.13 Interventions for Sarcopenia
12.14 How to Provide Resistance Training
12.15 How to Provide Amino Acids and Protein for Persons with Sarcopenia
12.16 Pharmacological Treatment of Sarcopenia
12.17 Conclusions
References
Chapter 13: Osteoporosis and Cellular Senescence in Bone
13.1 Introduction
13.2 Role of Bone Cells and Age-Related Changes
13.3 Cellular Senescence in the Bone Microenvironment
13.4 Bone Phenotype in Animal Models of Accelerated Senescence
13.4.1 DNA Damage
13.4.2 Telomere Shortening
13.5 Cellular Senescence in Bone
13.6 Elimination of Senescent Cells in Bone Using Transgenic Mice
13.7 Senolytic and Senomorphic Approaches to Treating Osteoporosis
13.8 Summary
References
Chapter 14: Aging and Chronic Kidney Disease Viewed from the FGF-Klotho Endocrine System
14.1 Discovery of the Klotho Gene
14.2 Klotho Protein Function
14.3 Discovery of the FGF-Klotho Endocrine Axes
14.4 Phosphate and CKD
14.5 Phosphate Accelerates Aging
14.6 Calciprotein Particles (CPPs)
14.7 CPPs and Lipoproteins
14.8 Secreted αKlotho
14.9 FGF21-βKlotho Endocrine System
14.10 FGF21 and CKD
14.11 Concluding Remarks
References
Chapter 15: Aging Biomarker SMP30 into a New Phase of Vitamin C and Aging Research
15.1 Introduction
15.2 Discovery of Age-Associated Protein SMP30
15.3 Functional Analysis of SMP30
15.4 SMP30 as an Organophosphatase
15.5 SMP30 Homolog in Fireflies
15.6 SMP30 Deficiency
15.7 SMP30 Is a Gluconolactonase (GNL)
15.8 SMP30-Knockout Mice Are Unable to Synthesize Vitamin C
15.9 Vitamin C Deficiency Accelerates Aging
15.10 Rough Estimation of Vitamin C Level That Accelerates Human Aging
15.11 Currently Available Findings Using SMP30-Knockout Mice
15.12 Perspectives of Vitamin C and Aging Research Using SMP30-Knockout Mice
References
Part V: Aging Brain: Cognitive Decline, Synaptic Plasticity
Chapter 16: Age-Related Memory Impairments Are Caused by Alterations in Glial Activity at Old Ages
16.1 Associative Memory in Drosophila and the Effects of Aging on Memory
16.2 Age-Related Impairments in MTM
16.3 Age-Related Impairments in LTM
16.4 Defects in Neuron-Glia Interactions in Mammalian Models
References
Chapter 17: Critical Roles of Glial Neuroinflammation in Age-Related Memory Decline
17.1 Introduction
17.2 Age-Related Cognitive Decline in Animal Models
17.2.1 Cognitive Declines in Animal Model for Vascular Dementia
17.2.2 Memory Declines in Mouse Model for Alzheimer´s Disease
17.3 Critical Roles of Neuroinflammation in Age-Related Cognitive declines
17.3.1 Glial Neuroinflammation
17.3.2 Neuroinflammation at the Cerebrovascular Unit
17.4 Age-Related Cognitive Decline in Elderly Individuals
17.5 Conclusion
References
Chapter 18: Central Mechanisms Linking Age-Associated Physiological Changes to Health Span Through the Hypothalamus
18.1 Introduction
18.2 Molecules and Signaling Pathways in the Hypothalamus that Control Mammalian Longevity
18.2.1 Sirtuin
18.2.2 Mechanistic Target of Rapamycin
18.2.3 Nuclear Factor-κB
18.2.4 Hypothalamic Stem Cells
18.2.5 Temperature-Sensitive Neurons
18.2.6 Neurons in the Arc
18.3 Potential Common Mechanisms of Aging and Longevity via the Hypothalamus
18.4 Perspective
References
Part VI: Aged Brain: Neurodegenerative Diseases
Chapter 19: PET Imaging of Amyloid and Tau in Alzheimer´s Disease
19.1 Introduction
19.2 Amyloid PET Imaging
19.3 Tau PET Imaging
19.4 Conclusions
References
Chapter 20: Presenilin/γ-Secretase in the Pathogenesis of Alzheimer´s Disease
20.1 Introduction
20.2 Identification of Presenilins as an Important Factor for γ-Secretase
20.3 Regulation of γ-Secretase Activities as a Potential Therapeutic Strategy
20.4 Intramembrane Proteolysis and Presenilin Structure
20.5 Perspectives
References
Chapter 21: Amyloid-β in Brain Aging and Alzheimer´s Disease
21.1 Introduction
21.2 Catabolism, Anabolism, and Clearance of Aβ
21.3 Amyloid Pathologies and AD
21.4 Animal Models to Study Amyloid Pathology and Aging
21.5 Conclusions
References
Chapter 22: Tau Pathology and Neurodegenerative Disorders
22.1 Development of Tau Pathology
22.2 Mechanism of Tau Aggregation
22.3 Tau Pathology and Brain Dysfunction
22.4 Therapies to Target Tau
References
Chapter 23: Aging and Parkinson´s Disease: Pathological Insight on Model Mice
23.1 Introduction
23.2 Change of Dopaminergic Neurons in PD
23.3 Age-Related Pathogenesis of PD
23.3.1 Oxidative Stress
23.3.2 Mitochondria Dysfunction
23.3.3 Protein Degradation
23.3.4 REST Localization
23.3.5 Change of Dopaminergic Neurons in Aged Human and Mouse
23.3.6 Locomotor Impairment of Aged C57BL/6 Mice
23.3.7 Tyrosine Hydroxylase Neuron Number Decreases in Aged Mice, Which Contributes to Their Locomotor Dysfunction
23.3.8 Accumulation of Fragmented Mitochondria in Aged Mice
23.4 PD Model Mice
23.4.1 Dopaminergic Neuron-Specific Atg7-Deficient Mice
23.4.1.1 Characterization of Locomotor Impairments
23.4.1.2 Age-Related Development of p62 Inclusions in the Dopaminergic Neuron
23.4.2 p62-Positive Inclusions Contain Endogenous Synuclein
23.4.2.1 Abundance of Tyrosine Hydroxylase Neurons Is Reduced in Aged Atg7flox/flox:TH-Cre Mice
23.4.3 Parkin-Deficient Mice
23.4.3.1 Locomotor Impairments of Aged Parkin Knockout Mice
23.4.3.2 Mitochondrial Fragmentation in Dopaminergic Neuron
23.4.3.3 Accumulation of Damaged Mitochondria
23.4.3.4 Abundance of Tyrosine Hydroxylase Neurons Is Reduced in Aged Parkin Knockout Mice
23.4.4 CHCHD2-Deficient Mice
23.4.4.1 Locomotor Impairments of Aged CHCHD2 Knockout Mice
23.4.4.2 Age-Related Development of Inclusions Are Associated with Mitochondria Function
23.4.4.3 Abundance of Tyrosine Hydroxylase Neurons Is Reduced in Aged CHCHD2 Knockout Mice
23.5 Conclusion
References
Part VII: Anti-aging: Intervention and Epidemiology
Chapter 24: Evaluating the Brain Aging Through Eyes: The Potential Use of Hyperspectral Imaging Cameras to Diagnose Alzheimer´...
24.1 Introduction
24.2 The Retina as a ``Window into the Brain´´
24.3 Retinal Findings on OCT Fundus Examination in AD and MCI
24.4 Detection of Amyloid Beta and Phosphorylated Tau in the Retina of AD Patients
24.5 Noninvasive Imaging of the Retina Using Hyperspectral Imaging Cameras
24.6 Significance of Retinal Amyloid β Detection: Expectations and Cautions for Dementia Risk Assessment
24.7 Perspectives
References
Chapter 25: Healthy Aging in Japan
25.1 Introduction
25.2 Extension of Life Span
25.2.1 Life Span
25.2.2 HALE
25.3 Redefining the Older Adults in Japan
25.3.1 Changes in Physical Functions with Age
25.3.2 Age-Related Changes in Intelligence
25.3.3 New Definition of the Older Adults
25.4 Why the Japanese Live Longer
25.4.1 Genetic Factors
25.4.1.1 Longevity-Related Genes in Japanese
25.4.1.2 Apolipoprotein E (APOE) Genotype
25.4.1.3 Gene-Environment Interaction
25.4.2 Obesity and Dietary Habits
25.4.2.1 Obesity
25.4.2.2 Traditional Japanese Diet
25.4.2.3 Alcohol and Longevity
25.4.3 Social Factors
25.5 Conclusion
References
Name Index
Subject Index