فهرست مطالب
Preface
Contents
Chapter 1: Introduction: Historical Development and Progression of Clinical Research on Ageing
Introduction
From Early Civilizations to the Age of Enlightenment
Modern Ageing Research
Evolutionary Theories of Ageing
Molecular Research on Ageing
Geroscience: An Integrative Approach
Clinical Research on Ageing
Challenges for Future Trials
Final Remarks
References
Chapter 2: Bone Cells Metabolic Changes Induced by Ageing
Introduction
Bone Cells and Ageing
Osteoblasts and Ageing
Osteoclasts and Ageing
Osteocytes and Ageing
Multipotent Mesenchymal Stem Cells and Ageing
Concluding Remarks
References
Chapter 3: Chronic Inflammation as an Underlying Mechanism of Ageing and Ageing-Related Diseases
Introduction
Key Factors Influencing Chronic Inflammation in Ageing
Pro- and Anti-inflammatory Cytokines and SASP
Changes in Endogenous Anti-inflammatory Lipid Mediators During Ageing
Crucial Role of Oxidative Stress in Age-Related Chronic Inflammation
Molecular and Cellular Constituents in Inflammation-Related Pathophysiological Conditions
NF-κB Involvement
Inflammasome in Chronic Inflammation
Role of Autophagy in Inflammation
Senoinflammation Schema: Exacerbation by SASP and Suppression by Calorie Restriction (CR)
Conclusion
References
Chapter 4: Heart Disease and Ageing: The Roles of Senescence, Mitochondria, and Telomerase in Cardiovascular Disease
Introduction: Cardiovascular Ageing
Cardiovascular Ageing and Atherosclerosis
Ageing and Heart Failure
Ageing and Cardiothoracic Surgery
Senescence as a Driver of Cardiovascular Disease
Mitochondrial Dysfunction and Oxidative Stress
Telomeres and Telomerase in Cardiovascular Disease, Replicative Senescence and Beyond
Mitochondrial Dysfunction of T Lymphocytes as a Potential Mechanism of Enhanced Inflammation Post-myocardial Infarction
Inflammation Is an Important Residual Risk Post-myocardial Infarction
Mitophagy and Age-Related Cardiovascular Disease
Accelerated Ageing and Cardiovascular Disease: Chemotherapy-Induced Cardiotoxicity
Viral Infection, Inflammation, Senescence, and Cardiovascular Disease
References
Chapter 5: Chronic Kidney Disease and the Exposome of Ageing
Introduction
Ageing Is a Process
A Geroscience Approach to Age-Related Disease
Modelling Ageing Using the Kidney
Phosphate Biology
Modulating the Exposome to Treat CKD
Future Treatment Strategies
References
Chapter 6: Sarcopenia and Ageing
Ageing
Sarcopenia
Clinical Signs, Symptoms, and Screening
Diagnosis
Prevalence
Pathogenesis of Sarcopenia
Mitochondrial Dysfunction
Intramuscular Fat Infiltration
Neuromuscular Junction Deterioration
Current Treatments
Aerobic Exercises
Resistance Exercises
Nutritional Supplementation
Conclusions and Future Directions
References
Chapter 7: Tendon Aging
Introduction
Aging Hallmarks
Tendon Tissues
Tendon Structure and Composition
Tendon Vasculature
Tendon Biomechanical Properties
Tendon Cell Types
Characteristics of Aged Tendon Tissue
Effects of Aging on Tendon Structure and Mechanical Properties
Age-Related Changes in Tendon Cells
Aging and Tendon Diseases
Future Perspectives
Concluding Remarks
References
Chapter 8: Virus Infections in Older People
Introduction
Comprehensive Geriatric Assessment
Functional Status
Mobility
Cognition
Mood Disorders
Polypharmacy
Social Factors
Nutritional Status
Sensory Impairment
Social Factors
Specific Viral Infections
Respiratory Syncytial Virus (RSV)
Transmission
Symptoms
Severe RSV Infection
RSV Prevention
Diagnosis
Treatment
COVID-19
Introduction
Background
Pathophysiology
Symptoms
Diagnosis and Testing
Treatment
Vaccination
Specific Considerations in Older People
Influenza
Influenza in Older People
Pathogenesis
Risk Factors
Presentation
Differential Diagnosis
Investigations
Management
General Measures
Pharmacological
Complications
Norovirus
Introduction
Epidemiology
Norovirus in Older Adults
Long-Term Care Facilities and Infection Risk
Prevention
Vaccine
Hepatitis
Introduction
Differences in Older People
Vaccinations
Management
Varicella Zoster
Introduction
Epidemiology
Clinical Presentation
Complications
Treatment
Herpes Simplex
Dengue
Pathogenesis
Clinical Features
Diagnostic Testing
Investigations
Management
Prognosis
Prevention
Dengue in Older People
References
Chapter 9: Models and Biomarkers for Ovarian Ageing
Introduction
Physiological and Endocrine Biomarkers
Genetic and Subcellular Biomarkers
Conclusions
References
Chapter 10: Ageing and the Autonomic Nervous System
Introduction
Temporal Changes in the Nervous System
Temporal Changes in the Gross Anatomy of the Nervous System
Temporal Changes in the Morphological Arrangement of the Nervous System
Temporal Changes in the Morphological Structure of Individual Neurons
Temporal Changes in the Chemical Composition of Individual Neurons
Age-Related Biochemical Changes in Individual Neurons
Age-Related Changes in Intraneuronal Organelle Dynamics
Ageing and Neuronal Autophagy
Ageing and Neuronal Mitochondrial Function
Age-Related Changes in Intraneuronal Metabolism
Age-Related Changes in Intraneuronal Ca2+ Homeostasis
Age-Related Changes in Neuronal Oxidative Stress
Age-Related Changes in Extraneuronal Neurotrophic Signalling
Age-Related Changes in Extraneuronal Inflammation
The Autonomic Nervous System (ANS) as a Paradigm
The Evolutionary Origins of the ANS
The Gross Anatomy of the ANS
The ANS and the GI Tract
Age-Related Changes in ANS Anatomy
Age-Related Changes in the Biochemistry of Individual ANS Neurons
The Impact of Age-Related Neuronal Changes on ANS Function
Age and ANS Control of Lens Refractive Index
Age and ANS Control of Ventilation
Age and ANS Control of ABP
Age and ANS Control of CO
Age and ANS Control of TPR and Local Vascular Mechanisms
Age and ANS Control of HR
Age and the Interaction Between the ANS and Immunity
The Clinical Implications of Age-Related Changes in the ANS
The Ageing ANS and Autonomic Failure
The Ageing ANS and Neurocardiogenic Syncope
Orthostatic Hypotension
Carotid Sinus Hypersensitivity
Cerebral Autoregulation
The Ageing ANS and GI Dysfunction
The Ageing ANS and Urinary Incontinence
The Ageing ANS and Erectile Dysfunction
The Ageing ANS and Thermoregulation
The Ageing ANS and Sepsis
The Ageing ANS and Peri-Operative Care
Conclusions
References
Chapter 11: Astrocytes in Ageing
Brain Ageing, Cognitive Reserve and Neuroglia
Astrocytes and the Brain Active Milieu
Protoplasmic Astrocytes
Ageing and Morphological Decline of Astrocytes
Physiology of Old Astrocytes
Functional Decline of Ageing Astrocytes
Neurotransmitter Homeostasis
Neuroglio-Vascular Unit and the Blood-Brain Barrier
Neurogenesis
Age-Dependent Decline of the Glymphatic System
Ageing Impairs Astroglial Metabolic Support
Ageing and Astrocytic Mitochondria
Cholesterol Synthesis
Age-Dependent Decline of Astroglial Neuroprotection
Conclusions
References
Chapter 12: Hearing and Ageing
Introduction
Peripheral Hearing Loss
Genetics
Noise Exposure
Central Hearing Loss
The Effect of Hearing Rehabilitation on Brain and Cellular Functions
Histopathology of the Ageing Ear
Conclusions
References
Chapter 13: Melatonin and Aging
Introduction
Melatonin and Diseases Where Aging Is a Potential Comorbidity
Cancer
Alzheimer´s Disease (AD)
Diabetes
Cardiac Disease, Cerebrovascular Disease
Frailty
SARS-CoV-2
Pathways Contributing to the Multiplicity of Melatonin Actions
The Centrality of Receptor Activation
Selectivity of Melatonin Engagement
Discussion and Conclusion
References
Chapter 14: Protein and Energy Supplements for the Elderly
Introduction
General Structure of Proteins
Protein Turnover
Protein Turnover in Aging
Amino Acid Metabolism
Amino Acid Metabolism in the Elderly
Protein Changes in Aging
Loss of Proteostasis
Sarcopenia
Changes in Collagen Fibers
Changes in Elastin Fibers
Amino Acid Supplementation in the Elderly
Creatine Supplementation in the Elderly
Vitamin and Mineral Supplementation in the Elderly
Vitamin Supplementation
Mineral Supplementation
Conclusion
References
Chapter 15: Ageing, Metabolic Dysfunction, and the Therapeutic Role of Antioxidants
Introduction
Adipose Tissue and the Pathophysiology of Obesity
Ageing and Age-Related Diseases
Mechanistic Similarities Between Ageing and Obesity
Oxidative Stress and Inflammation in Ageing and Obesity
Hallmarks of Ageing in Obesity
Genomic Instability
Telomere Attrition
Epigenetic Alterations
Loss of Proteostasis
Cellular Senescence
Mitochondrial Dysfunction
Deregulated Nutrient Sensing
Stem Cell Exhaustion
Altered Intercellular Communication
Dietary Interventions Against Ageing, Age-Related Diseases, and Metabolic Syndrome
Nutraceuticals
Curcumin
Epigallocatechin Gallate
Resveratrol
Quercetin
Anthocyanins
Diets
Mediterranean Diet
Dietary Approaches to Stop Hypertension Diet
Mediterranean-DASH Intervention for Neurodegenerative Delay Diet
Fasting Regimes
The Longevity Diet
Conclusions
References
Chapter 16: Clinical Ageing
Introduction
Ageing, a Systems-Biology Approach
The Impact of Ageing and Age-Related Comorbidities on Stroke Outcome in Animal Models and Humans
Obesity and Ageing
Insulin Resistance and Ageing
Organ Failure During Ageing
Ageing of the HPA Axis and Drugs That Can Regulate It
Ageing, Cerebrovascular Diseases and Regeneration
Clinical Studies
Plasma Biomarkers Associated with Ischaemic Stroke
Neurovascular Unit-Derived Exosomes in Response to Stroke
References
Contents
Chapter 1: Introduction: Historical Development and Progression of Clinical Research on Ageing
Introduction
From Early Civilizations to the Age of Enlightenment
Modern Ageing Research
Evolutionary Theories of Ageing
Molecular Research on Ageing
Geroscience: An Integrative Approach
Clinical Research on Ageing
Challenges for Future Trials
Final Remarks
References
Chapter 2: Bone Cells Metabolic Changes Induced by Ageing
Introduction
Bone Cells and Ageing
Osteoblasts and Ageing
Osteoclasts and Ageing
Osteocytes and Ageing
Multipotent Mesenchymal Stem Cells and Ageing
Concluding Remarks
References
Chapter 3: Chronic Inflammation as an Underlying Mechanism of Ageing and Ageing-Related Diseases
Introduction
Key Factors Influencing Chronic Inflammation in Ageing
Pro- and Anti-inflammatory Cytokines and SASP
Changes in Endogenous Anti-inflammatory Lipid Mediators During Ageing
Crucial Role of Oxidative Stress in Age-Related Chronic Inflammation
Molecular and Cellular Constituents in Inflammation-Related Pathophysiological Conditions
NF-κB Involvement
Inflammasome in Chronic Inflammation
Role of Autophagy in Inflammation
Senoinflammation Schema: Exacerbation by SASP and Suppression by Calorie Restriction (CR)
Conclusion
References
Chapter 4: Heart Disease and Ageing: The Roles of Senescence, Mitochondria, and Telomerase in Cardiovascular Disease
Introduction: Cardiovascular Ageing
Cardiovascular Ageing and Atherosclerosis
Ageing and Heart Failure
Ageing and Cardiothoracic Surgery
Senescence as a Driver of Cardiovascular Disease
Mitochondrial Dysfunction and Oxidative Stress
Telomeres and Telomerase in Cardiovascular Disease, Replicative Senescence and Beyond
Mitochondrial Dysfunction of T Lymphocytes as a Potential Mechanism of Enhanced Inflammation Post-myocardial Infarction
Inflammation Is an Important Residual Risk Post-myocardial Infarction
Mitophagy and Age-Related Cardiovascular Disease
Accelerated Ageing and Cardiovascular Disease: Chemotherapy-Induced Cardiotoxicity
Viral Infection, Inflammation, Senescence, and Cardiovascular Disease
References
Chapter 5: Chronic Kidney Disease and the Exposome of Ageing
Introduction
Ageing Is a Process
A Geroscience Approach to Age-Related Disease
Modelling Ageing Using the Kidney
Phosphate Biology
Modulating the Exposome to Treat CKD
Future Treatment Strategies
References
Chapter 6: Sarcopenia and Ageing
Ageing
Sarcopenia
Clinical Signs, Symptoms, and Screening
Diagnosis
Prevalence
Pathogenesis of Sarcopenia
Mitochondrial Dysfunction
Intramuscular Fat Infiltration
Neuromuscular Junction Deterioration
Current Treatments
Aerobic Exercises
Resistance Exercises
Nutritional Supplementation
Conclusions and Future Directions
References
Chapter 7: Tendon Aging
Introduction
Aging Hallmarks
Tendon Tissues
Tendon Structure and Composition
Tendon Vasculature
Tendon Biomechanical Properties
Tendon Cell Types
Characteristics of Aged Tendon Tissue
Effects of Aging on Tendon Structure and Mechanical Properties
Age-Related Changes in Tendon Cells
Aging and Tendon Diseases
Future Perspectives
Concluding Remarks
References
Chapter 8: Virus Infections in Older People
Introduction
Comprehensive Geriatric Assessment
Functional Status
Mobility
Cognition
Mood Disorders
Polypharmacy
Social Factors
Nutritional Status
Sensory Impairment
Social Factors
Specific Viral Infections
Respiratory Syncytial Virus (RSV)
Transmission
Symptoms
Severe RSV Infection
RSV Prevention
Diagnosis
Treatment
COVID-19
Introduction
Background
Pathophysiology
Symptoms
Diagnosis and Testing
Treatment
Vaccination
Specific Considerations in Older People
Influenza
Influenza in Older People
Pathogenesis
Risk Factors
Presentation
Differential Diagnosis
Investigations
Management
General Measures
Pharmacological
Complications
Norovirus
Introduction
Epidemiology
Norovirus in Older Adults
Long-Term Care Facilities and Infection Risk
Prevention
Vaccine
Hepatitis
Introduction
Differences in Older People
Vaccinations
Management
Varicella Zoster
Introduction
Epidemiology
Clinical Presentation
Complications
Treatment
Herpes Simplex
Dengue
Pathogenesis
Clinical Features
Diagnostic Testing
Investigations
Management
Prognosis
Prevention
Dengue in Older People
References
Chapter 9: Models and Biomarkers for Ovarian Ageing
Introduction
Physiological and Endocrine Biomarkers
Genetic and Subcellular Biomarkers
Conclusions
References
Chapter 10: Ageing and the Autonomic Nervous System
Introduction
Temporal Changes in the Nervous System
Temporal Changes in the Gross Anatomy of the Nervous System
Temporal Changes in the Morphological Arrangement of the Nervous System
Temporal Changes in the Morphological Structure of Individual Neurons
Temporal Changes in the Chemical Composition of Individual Neurons
Age-Related Biochemical Changes in Individual Neurons
Age-Related Changes in Intraneuronal Organelle Dynamics
Ageing and Neuronal Autophagy
Ageing and Neuronal Mitochondrial Function
Age-Related Changes in Intraneuronal Metabolism
Age-Related Changes in Intraneuronal Ca2+ Homeostasis
Age-Related Changes in Neuronal Oxidative Stress
Age-Related Changes in Extraneuronal Neurotrophic Signalling
Age-Related Changes in Extraneuronal Inflammation
The Autonomic Nervous System (ANS) as a Paradigm
The Evolutionary Origins of the ANS
The Gross Anatomy of the ANS
The ANS and the GI Tract
Age-Related Changes in ANS Anatomy
Age-Related Changes in the Biochemistry of Individual ANS Neurons
The Impact of Age-Related Neuronal Changes on ANS Function
Age and ANS Control of Lens Refractive Index
Age and ANS Control of Ventilation
Age and ANS Control of ABP
Age and ANS Control of CO
Age and ANS Control of TPR and Local Vascular Mechanisms
Age and ANS Control of HR
Age and the Interaction Between the ANS and Immunity
The Clinical Implications of Age-Related Changes in the ANS
The Ageing ANS and Autonomic Failure
The Ageing ANS and Neurocardiogenic Syncope
Orthostatic Hypotension
Carotid Sinus Hypersensitivity
Cerebral Autoregulation
The Ageing ANS and GI Dysfunction
The Ageing ANS and Urinary Incontinence
The Ageing ANS and Erectile Dysfunction
The Ageing ANS and Thermoregulation
The Ageing ANS and Sepsis
The Ageing ANS and Peri-Operative Care
Conclusions
References
Chapter 11: Astrocytes in Ageing
Brain Ageing, Cognitive Reserve and Neuroglia
Astrocytes and the Brain Active Milieu
Protoplasmic Astrocytes
Ageing and Morphological Decline of Astrocytes
Physiology of Old Astrocytes
Functional Decline of Ageing Astrocytes
Neurotransmitter Homeostasis
Neuroglio-Vascular Unit and the Blood-Brain Barrier
Neurogenesis
Age-Dependent Decline of the Glymphatic System
Ageing Impairs Astroglial Metabolic Support
Ageing and Astrocytic Mitochondria
Cholesterol Synthesis
Age-Dependent Decline of Astroglial Neuroprotection
Conclusions
References
Chapter 12: Hearing and Ageing
Introduction
Peripheral Hearing Loss
Genetics
Noise Exposure
Central Hearing Loss
The Effect of Hearing Rehabilitation on Brain and Cellular Functions
Histopathology of the Ageing Ear
Conclusions
References
Chapter 13: Melatonin and Aging
Introduction
Melatonin and Diseases Where Aging Is a Potential Comorbidity
Cancer
Alzheimer´s Disease (AD)
Diabetes
Cardiac Disease, Cerebrovascular Disease
Frailty
SARS-CoV-2
Pathways Contributing to the Multiplicity of Melatonin Actions
The Centrality of Receptor Activation
Selectivity of Melatonin Engagement
Discussion and Conclusion
References
Chapter 14: Protein and Energy Supplements for the Elderly
Introduction
General Structure of Proteins
Protein Turnover
Protein Turnover in Aging
Amino Acid Metabolism
Amino Acid Metabolism in the Elderly
Protein Changes in Aging
Loss of Proteostasis
Sarcopenia
Changes in Collagen Fibers
Changes in Elastin Fibers
Amino Acid Supplementation in the Elderly
Creatine Supplementation in the Elderly
Vitamin and Mineral Supplementation in the Elderly
Vitamin Supplementation
Mineral Supplementation
Conclusion
References
Chapter 15: Ageing, Metabolic Dysfunction, and the Therapeutic Role of Antioxidants
Introduction
Adipose Tissue and the Pathophysiology of Obesity
Ageing and Age-Related Diseases
Mechanistic Similarities Between Ageing and Obesity
Oxidative Stress and Inflammation in Ageing and Obesity
Hallmarks of Ageing in Obesity
Genomic Instability
Telomere Attrition
Epigenetic Alterations
Loss of Proteostasis
Cellular Senescence
Mitochondrial Dysfunction
Deregulated Nutrient Sensing
Stem Cell Exhaustion
Altered Intercellular Communication
Dietary Interventions Against Ageing, Age-Related Diseases, and Metabolic Syndrome
Nutraceuticals
Curcumin
Epigallocatechin Gallate
Resveratrol
Quercetin
Anthocyanins
Diets
Mediterranean Diet
Dietary Approaches to Stop Hypertension Diet
Mediterranean-DASH Intervention for Neurodegenerative Delay Diet
Fasting Regimes
The Longevity Diet
Conclusions
References
Chapter 16: Clinical Ageing
Introduction
Ageing, a Systems-Biology Approach
The Impact of Ageing and Age-Related Comorbidities on Stroke Outcome in Animal Models and Humans
Obesity and Ageing
Insulin Resistance and Ageing
Organ Failure During Ageing
Ageing of the HPA Axis and Drugs That Can Regulate It
Ageing, Cerebrovascular Diseases and Regeneration
Clinical Studies
Plasma Biomarkers Associated with Ischaemic Stroke
Neurovascular Unit-Derived Exosomes in Response to Stroke
References
