Sleep and Clocks in Aging and Longevity

Preface
Contents
Part I Understanding Sleep and Clock Interlink in Health and Longevity
1 Sleep and Circadian Clock: Novel Players in Health Impacts and Aging
1.1 Introduction
1.2 Sleep
1.2.1 What is Sleep?
1.2.2 Physiological Basis of Sleep
1.2.3 Types of Sleep/Different Stages of Sleep
1.2.4 Sleep Duration/Need
1.2.5 Regulation of Sleep
1.3 Biological Clock: Circadian Timing System (CTS)
1.3.1 SCN: Neurotransmitters in Input and Output Pathways
1.3.2 SCN: Relay Center for Information
1.3.3 Melatonin: Messenger of Darkness
1.3.4 Molecular Components of CTS
1.4 Sleep and Circadian Rhythms: Interplay
1.4.1 The Two-Process Model: The Interaction of Circadian Forces and Sleep Homeostasis
1.4.2 Sleep Gate
1.5 Sleep and Clock Misalignment with Aging
1.5.1 Alterations in Sleep Structure in Old
1.5.2 Desynchronization of Circadian Rhythm Patterns in Old
1.5.3 The Circadian and Sleep Perturbances
1.6 Interventions to Improve Sleep and Clock Function: A Step Toward Healthy Aging and Longevity
1.6.1 Sleep Hygiene
1.6.2 Light Therapy
1.6.3 Administration of Exogenous Melatonin
1.6.4 Herbal and Other Interventions
1.7 Goals and Conclusions
References
2 Cells and Circuits of the Suprachiasmatic Nucleus and the Control of Circadian Behaviour and Sleep
2.1 Introduction: Mammalian Circadian System Overview
2.2 Molecular-Genetic and Cellular Basis of Circadian Timekeeping in Mammals
2.2.1 The Core Feedback Loop—Genes and Molecules: Discoveries Through Mapping and Mutagenesis Screens
2.2.2 Additional Feedback Loops Support the TTFL
2.2.3 Control of the Stability of Clock Proteins and Effect on Behaviour
2.3 Circadian Properties of SCN Neurons
2.3.1 Observing Clock Proteins at the Cellular Level
2.3.2 SCN Neural Activity and Transcriptional Cycles
2.3.3 The Importance of Coupling Between SCN Neurons
2.4 Circuit Architecture of the SCN as a Neuronal Network
2.4.1 Entrainment of the SCN Network: Photic and Non-photic Cues
2.4.2 SCN Network Synchrony: GABA and Neuropeptides
2.4.3 VIP Axis: Mediator of SCN Photic Entrainment and Neuronal Synchrony
2.4.4 GRP Axis: An Accessory Entrainment and Synchronisation Pathway
2.4.5 AVP Axis: Within-Shell Coupling and Circadian Output
2.4.6 Prokineticin-2 Axis: More Than an SCN Output?
2.4.7 An Emerging View of the Functional Topology of the SCN Network
2.5 The Role of Astrocytes in the SCN
2.5.1 Astrocytic Control of Circadian Rhythms
2.5.2 Astrocyte-To-Neuron-To-Astrocyte Communication Within the SCN Network
2.6 SCN Outputs and Control of Circadian Behaviour and Sleep
2.6.1 SCN Outputs and Control of Circadian Behaviour
2.6.2 SCN in the Circadian Regulation of Sleep
2.7 Conclusion and Future Perspectives
References
3 Circadian Regulation of Sleep
3.1 Introduction
3.2 The Circadian Clock System
3.3 Regulation of Sleep—Two-Process Model
3.4 Homeostatic Regulation of Sleep
3.5 Circadian Regulation of Sleep
3.5.1 Role of the SCN in Sleep Regulation
3.5.2 Regulation of Sleep by Canonical Circadian Clock Genes
3.6 Effects of Circadian Misalignment on Aging
3.6.1 Attenuation of Circadian Rhythms with Aging
3.6.2 Acceleration of Aging by Circadian Misalignment/Disruption
3.7 Effects of Sleep Disorders on Aging
3.7.1 Age-Related Sleep Changes
3.7.2 Acceleration of Aging by Sleep Disorders
3.8 Concluding Remarks
References
4 Age-Related Decline in the Central Circadian Clock
4.1 Introduction
4.2 Effects of Aging on Circadian Rhythms
4.3 The Central Circadian Clock in the SCN
4.4 Age-Related Decline in Circadian Rhythms Caused by SCN Disorganization
4.5 Age-Related Dysfunction of SCN Outputs
4.6 Mechanisms Underlying SCN Output Dysfunction
4.7 Conclusion
References
5 Impact of Cellular Senescence on Cellular Clocks
5.1 Introduction
5.2 Evidence that Cellular Senescence Is a Causative Factor for the Different Age-Related Diseases
5.3 Characteristics of Senescent Cells
5.4 Permanent Cell Cycle Arrest in Senescent Cells
5.5 Altered Signaling Pathways in Cellular Senescence
5.5.1 AMPK Signaling
5.5.2 P38 MAPK Signaling
5.5.3 NF-κB Signaling Pathway
5.5.4 mTOR Signaling Pathway
5.5.5 Unfolding Protein Response (UPR) Pathway
5.5.6 Cyto- and Nucleo-Skeletons
5.6 Metabolic Changes in Cellular Senescence
5.6.1 Adenosine Triphosphate (ATP)
5.6.2 Nicotinamide Adenine Dinucleotide (NAD+)
5.6.3 Polyamines
5.7 The Circadian Clock
5.8 Aging of the Circadian Clock
5.9 Possible Molecular Regulators of Cellular Clocks in Senescent Cells
5.9.1 P53 Signaling Pathway
5.9.2 AMPK Signaling
5.9.3 P38 MAPK Signaling
5.9.4 NF-κB Signaling Pathway
5.9.5 mTOR Signaling Pathway
5.9.6 Unfolding Protein Response Pathway
5.9.7 Cyto- and Nucleo-Skeletons
5.9.8 NAD+ and NAD+/NADH Ratio
5.9.9 Polyamines
5.10 Conclusions
References
Part II Sleep, Ageing and Longevity
6 Optimum Sleep for Healthy Ageing
6.1 Sleep and Wakefulness
6.2 Cardiovascular and Respiratory Dysfunctions Associated with Sleep Loss
6.3 Endocrine Dysfunctions Associated with Sleep Loss
6.4 Metabolic Dysfunctions and Sleep Loss
6.5 Thermoregulatory Changes in Association with Sleep and Sleep Loss
6.6 Altered Immune Function in Relation to Sleep Disturbances
6.7 Cognitive Dysfunction in Association with Sleep Disturbances
6.8 Sleep Disturbances Associated with Changes in Social Factors
6.9 Ageing and Sleep Disturbances
6.10 Sleep Disturbances and Brain Maturity
6.11 Sleep Disorders in Association with Acute Diseases
6.12 Sleep Disorders in Association with Chronic Diseases
6.13 Summary and Conclusion
6.13.1 Sleep Disruptions as Basis of Many Disorders
6.13.2 NA, a Common Factor Responsible for Sleep Loss-Associated Pathophysiology
References
7 Healthy Brain Ageing and Longevity; the Harmony of Natural Products, APOE Polymorphism, and Melatonin
7.1 Apolipoprotein E (APOE) Polymorphism and Human Longevity
7.1.1 Population Ageing on Healthy Ageing
7.1.2 APOE Polymorphism and AD
7.2 Melatonin in Circadian Rhythms and Healthy Ageing
7.2.1 Melatonin in AD
7.2.2 Melatonin Via Plant-Based Diet
7.3 Antioxidant Properties of Tea
7.4 Protective Effect of Tea in AD Leading Towards Healthy Ageing
7.5 Therapeutic Potential of Cinnamon on AD
7.6 APOE and ACE Polymorphism in Human Longevity and the Protective Effect of Black Tea on AD-Related Neuropathologic Changes: A Proof of Concept
7.6.1 Sample Collection
7.6.2 Screening of AD-Related Neuropathologic Changes Using Histopathological and Immunohistochemical Techniques
7.6.3 Statistical Analysis
7.6.4 Major Findings
7.7 Future Perspectives
References
8 Role of Sleep in Imprinting Healthy Aging
8.1 Introduction
8.2 Maternal Sleep Loss During Pregnancy and Poor Health Consequences in F1 Generation
8.3 Dynamic Role of Sleep and Healthy Aging
8.4 Conclusion
References
9 Sleep, Ageing, and Cognitive Decline
9.1 Introduction
9.2 Age-Dependent Changes in Sleep Distribution and Oscillations
9.2.1 Age-Dependent Changes in Sleep
9.2.2 Age-Dependent Changes in Sleep Oscillations
9.2.3 Connection to Invertebrates
9.3 Consequences of Age-Dependent Sleep Loss
9.3.1 Glymphatic Clearance
9.3.2 Learning and Memory
9.4 Conclusions
References
Part III Clock, Ageing and Longevity
10 How Non-photic Cues for the Circadian Time System Matter in Healthy Aging
10.1 Introduction
10.1.1 Central and Peripheral Clocks: Categories of a Hierarchical System Model
10.1.2 Are Age-Altering Circadian Rhythms Consequences of Impaired Oscillators?
10.2 Light Versus Non-photic Zeitgebers
10.2.1 Photoentrainment and Aging
10.2.2 Feeding Time Entrains the Circadian Time Systems: Impact on Aging
10.2.3 Social Interactions Entrain the Circadian Time Systems: Impacts on Aging
10.3 Conclusion
References
11 Pineal Gland Physiology and Aging-Related Alterations in the Circadian Timing System
11.1 Introduction
11.2 Neuroendocrine Perspective of Circadian Rhythm and Aging
11.3 Changes in Sleep Pattern with Aging
11.4 The Relationship Between Aging Physiology and Circadian Rhythm
11.5 Aging and Circadian Rhythms
11.6 Modifications in Circadian Rhythms with Age
11.7 Amplitude and Circadian Organization
11.8 Entrainment and Responsiveness to Zeitgebers: Influence of Aging
11.9 Age-Associated Changes in Circadian Dysregulation
11.10 Conclusions
References
12 Circadian Rhythmicity in Aging and Parkinson’s Disease
12.1 Basal Ganglia
12.1.1 Parkinson’s Disease: A Major Basal Ganglia Disorder
12.1.2 The Neuroanatomical Basis of Parkinson’s Disease
12.2 Circadian Rhythmicity in Aging and PD
12.2.1 Role of BG and Clock Genes
12.2.2 Sleep and PD: The Intriguing Prelude
12.2.3 Rapid Eye Movement (REM) Sleep Behavior Disorder (RBD)
12.2.4 Stress
12.3 Factors Ascribing Longevity and Symptom Alleviation in PD
12.3.1 Relevance of Social Enrichment
12.3.2 Yoga
12.3.3 Healthy Living and Exercise
12.3.4 External Stimuli and the Imaginary World
12.3.5 Intermittent Fasting
12.4 Conclusion
References
Part IV Melatonin, Sleep and Clock
13 Sleep Hormone Melatonin, Inflammation and Aging
13.1 Introduction
13.2 Aging and Inflammation
13.3 Melatonin and Aging
13.4 Regulatory Effects of Melatonin on Aging
13.4.1 Melatonin Slows Aging Through Antioxidant Function
13.4.2 Melatonin Delays Aging by Repairing DNA Damage
13.4.3 Melatonin Promotes Autophagy and Reduces the Accumulation of Harmful Substances During Aging
13.4.4 Melatonin May Rescue Aging by Inhibiting Hyperactive Sympathetic Nerve Activity
13.4.5 Melatonin Regulates Infection and Delays Aging by Modulating Gut Microbiota
13.5 Conclusion
References
14 Melatonin as a Chronobiotic and Cytoprotector in Healthy Aging
14.1 Introduction
14.2 Inflammaging
14.3 The Circadian Apparatus
14.4 Melatonin as a Chronobiotic
14.5 Use of Melatonin in Aged Sleep
14.6 Melatonin and Inflammaging
14.7 Melatonin, Sirtuins, and the Anti-inflammatory Network
14.8 Therapeutic Value of Melatonin in Animal and Clinical Models of Age-Related NCDs
14.9 Concluding Remarks
References
15 Melatonin: A Saga of Health and Longevity
15.1 Introduction
15.2 Stress and Melatonin
15.3 Oxidative Stress and Melatonin
15.4 Melatonin in Immunomodulation
15.4.1 Melatonin and Immune Cells
15.4.2 Immunocompetent Cells and Melatonin Receptors
15.4.3 Anti-inflammatory Potential of Melatonin
15.5 Melatonin and Metabolic Health
15.5.1 Melatonin in the Protection of Cardiovascular Health
15.5.2 Melatonin and Diabetic Nephropathy
15.6 Bone Health (Osteoporosis and Osteoarthritis) and Melatonin
15.6.1 Osteoporosis and Melatonin
15.6.2 Melatonin and Osteoarthritis
15.7 Life Span Extending Benefits of Melatonin
15.7.1 Melatonin and Mitochondrial Health
15.7.2 Melatonin, Circadian Rhythm and Health
15.8 Phytomelatonin: A Natural Nutraceutical for Health
References
Part V Genetic Regulation of Sleep and Clock
16 Circadian Rhythm Manipulations: Implications on Behavioral Restoration in Central Nervous System Insults
16.1 Introduction
16.2 Circadian Rhythm Manipulation in Human Neurodegenerative Conditions
16.3 Evidence of Circadian Rhythm Manipulation to Restore Behavior and Cognition in Animal Models
16.4 Possible Underlying Mechanisms for the Potential Role of Circadian Manipulation on Behavior and Cognition
16.5 Conclusion
References
17 Epigenetics of Altered Circadian and Sleep Cycle Induced Effects on Aging and Longevity
17.1 Introduction
17.2 Circadian Rhythm: Regulation and Implications in Aging
17.3 Circadian Control of Sleep
17.3.1 Sleep Physiology
17.3.2 Sleep Architecture
17.3.3 Sleep Cycle Regulation
17.4 Sleep Dysregulation: Aging and Epigenetics
17.5 Epigentic Clock Theory and DNA Methylation
17.6 Heterochromatin Loss Model of Aging
17.7 Role of Non-coding RNA (NcRNA) in Aging
17.8 Histone Modifications in Aging Process
17.8.1 Histone Methylation in Aging
17.8.2 Histone Acetylation
17.8.3 Histone Deacetylation: Role of Sirtuins
17.9 Calorie Restriction: Rhythms and Implications in Aging
17.10 Sex Differences in Aging Epigenetics
17.11 Epigenetic Therapeutics
17.12 Concluding Remarks
References
18 Chronotype and Its Relation to Healthy Aging
18.1 Introduction
18.2 Chronotype and its Distribution among Population
18.3 Assessing the Chronotype
18.4 Chronotype and Variability in Biological Variables
18.5 Determinants of Chronotype
18.5.1 Endogenous Nature
18.5.2 Genetic Basis
18.6 Moderators of Chronotype
18.6.1 Age and Gender
18.6.2 Entrainment to Environmental Light/Geographical Region
18.6.3 Culture/Ethnicity/Work Schedule
18.7 Chronotype as Determinant of
18.7.1 Chronotype, Physical Activity and Sleep Health
18.7.2 Chronotype, Disease and Health Outcomes
18.7.3 Chronotype and Mental/cognitive Performances
18.7.4 Chronotype and Social Jetlag (Chronotypes and Circadian Desynchrony)
18.7.5 Chronotype with Reference to COVID-19 Pandemic
18.8 Summary and Recommendations
References
Part VI Therapeutic Interventions in Sleep Disorders and Clock Misalignment
19 Physical Exercise and Circadian Rhythm in Humans
19.1 Basic Characteristics of the Circadian System in Humans
19.2 Effects of Single-Bout Exercise on Circadian Rhythm in Humans
19.3 Effects of Repeated Exercise on the Circadian Rhythm in Humans
References
20 Circadian Rhythms and Time-Restricted Eating in Healthy Aging and Longevity
20.1 Introduction
20.2 Circadian Clock and Its Disruption with Aging
20.3 Time-Restricted Eating as a Novel Dietary Intervention
20.3.1 Circadian Rhythms, TRE, and Energy Metabolism
20.3.2 Time-Restricted Eating to Align with Circadian Rhythms for Healthy Aging
20.4 Conclusion
References
21 Achieving Healthy Aging in the Light-Polluted World
21.1 Introduction
21.2 Light Pollution—What Does It Mean?
21.3 Effects of Light Pollution on Human Circadian Organization
21.3.1 Desynchronization of the Circadian Rhythm by ALAN
21.3.2 ALAN Affects Pineal Gland Function
21.3.3 Misalignment of the Circadian System by Light Pollution
21.4 Light Pollution and Aging
21.4.1 Examples of Studies Involving Humans
21.4.2 Examples of Model Studies on Animals
21.5 Summary and Conclusion
References
22 Disruptions of Circadian Rhythms and Sleep/Wake Cycles in Neurologic Disorders
22.1 Introduction
22.2 Alzheimer’s Disease
22.3 Parkinson’s Disease
22.4 Huntington’s Disease
22.5 Stroke
22.6 Conclusion
References
23 Insomnia in the Elderly and Its Treatment
23.1 Definitions
23.2 Setting the Scene
23.2.1 Historical
23.2.2 Demographics
23.2.3 Socioeconomic Impact of Insomnia
23.3 Clinical Parameters
23.3.1 Diagnostic Tools
23.3.2 Comorbidities
23.3.3 Neurobiophysical and Cognitive Background of Insomnia
23.3.4 Nutrition and Insomnia
23.3.5 Thermoregulation and Insomnia
23.3.6 Behavioral and Physiological Conditions at Crosshairs
23.3.7 COVID-19 Pandemic and Insomnia
23.4 Therapy: A Broadband of Different Disciplines
23.4.1 The Light Therapy for Insomnia
23.4.2 Insomnia Pharmacology
23.5 Final Note
References
Part VII Experimental Models to Study Sleep and Clocks in Aging and Longevity
24 Invertebrate and Vertebrate Models in Sleep and Circadian Aging
24.1 Introduction
24.2 Changes in Sleep Quality and Circadian Rhythms Across Aging
24.3 Mice as a Model for Probing Sleep and Circadian Behaviors Across Aging
24.4 Non-mammalian Models of Sleep
24.5 Studying Sleep and Circadian Rhythms Across Aging in Zebrafish
24.6 Invertebrate Models for Sleep and Circadian Research Across Aging
24.7 Concluding Remarks
References
25 Melatonin, Circadian Rhythms, and Sleep: An Opportunity to Understand Mechanisms for Protecting Against Neurodegenerative Disease in Drosophila
25.1 Brief Introduction to Melatonin
25.2 Melatonin: Phase Marker and Chronobiotic
25.3 Melatonin’s Role in Sleep
25.4 A Primer on Reactive Oxygen Species
25.5 Melatonin: Innerworkings of a Powerful Antioxidant System
25.6 Melatonin: A Functionally Relevant Antioxidant
25.7 Melatonin: A Functionally Relevant Antioxidant, Part II
25.8 Do Discoveries Await in Drosophila?
25.9 Conclusion
References