Biochemistry and Cell Biology of Ageing: Part III Biomedical Science

Preface
Contents
About the Editors
Chapter 1: Introduction: Progression of the Science of Ageing
	Introduction
	References
Chapter 2: Chromatin Structure from Development to Ageing
	Introduction
	Nuclear Architecture
		The Nuclear Envelope
		Nuclear Lamina
		Chromosome Territories
	Chromatin 3D Organization and Dynamics
		Compartments
		Topologically Associated Domains (TADs)
		Lamina-Associated Domains (LADs)
	Chromatin Restructuring During Development
		DNA Methylation
		Histone Variants
		Histone Modifications
	Nuclear Remodeling in Development
		Lamins Regulate Nuclear Structure and Chromatin Organization During Development
		Programmed Cellular Senescence
	Chromatin Remodeling in Ageing
		Persistent Cellular Senescence
		Changes in Chromatin Structure and Histone Variants in Cellular Senescence
		DNA Methylation
		Histone Variants and Modifications
		Nuclear and 3D Genome Remodeling in Ageing
		The Role of Lamins in Regulating Chromatin Organization During Ageing
	Concluding Remarks
	References
Chapter 3: The Nuclear Envelope in Ageing and Progeria
	Introduction
	The Nuclear Lamina in Ageing and Premature Ageing Syndromes
	Nuclear Pore Complex Turnover and Decline in Ageing
	The Implication of Nucleocytoplasmic Transport in Neurodegenerative Disease
		RNA-Binding Proteins and Neurodegenerative Diseases
		Peptide Repeat Toxicity and NPC Function
		Additional Implications of NCT in Neurodegenerative Diseases
	Concluding Remarks
	References
Chapter 4: Mitochondrial DNA Mutations and Ageing
	Introduction
		Mitochondrial Structure and Function
		Oxidative Phosphorylation
		Mitochondrial Genetics
		Mitochondrial DNA Mutations in Ageing
			MtDNA Deletions
			MtDNA Point Mutations
		Mouse Models of Mitochondrial Alterations with Ageing
		Mitochondrial Function and Stem Cell Ageing
			MtDNA Mutations and Stem Cell Ageing
		Mitochondrial Regulation of the Ageing Immune System
		Targeting Mitochondria in Ageing
		Concluding Remarks
	References
5: The Proteasome and Ageing
	Introduction
	The Proteasome: A Brief Overview
	Cellular Senescence and the Proteasome
	Muscle Ageing and the Proteasome
	Skin Ageing and the Proteasome
	Brain Ageing and the Proteasome
	Proteasome and Age-Related Neurodegenerative Diseases
	Proteasome and Longevity
	Other Components of the Ubiquitin-Proteasome Pathway Implicated in Ageing
	Activating the Proteasome to Decelerate the Ageing Process
	Conclusion and Future Directions
	References
6: Gap Junctions and Ageing
	Introduction
		Gap Junctions and the Connexin Family
	Regulation of Gap Junctions at the Molecular Level
		Gene Structure and Transcription
		Translation
		Trafficking
		Posttranslational Modification of Connexins
	Heart
	Brain
	The Ocular System
	Bone
	Other Tissues
	Concluding Remarks
	References
Chapter 7: Cellular Senescence and Ageing
	What Is Cellular Senescence?
		History
		Characteristics and Markers
			Telomere Shortening
			DNA Damage
			SA-B-Gal
			Cyclin-Dependent Kinase Inhibitors
			Morphology
			Chromatin Alterations
			Lack of DNA Replication/Cell Proliferation
			SASP
	Types and Mechanisms of Cellular Senescence
		Replicative
		Stress-Induced
		Oncogene-Induced
		Bystander-Induced
		MiDAS
	In Vivo Relevance of Senescent Cells
		Cell Types and Tissues in Which Senescence Has Been Observed
		Age-Dependent Changes in the Abundance
	Senescence in Age-Related Disease
	Anti-senescent Interventions
		Pre-clinical Evidence
		Clinical Evidence
	Future Directions
		How to Better Target Senescent Cells?
		Important Considerations in Senolytics Treatments
	Concluding Remarks
	References
Chapter 8: Therapeutic Opportunities Presented by Modulation of Cellular Senescence
	What Is Cell Senescence?
	The Relationship Between Cell Senescence and Ageing
	Therapeutic Opportunities
		Osteoarthritis
		Kidney Dysfunction
		Liver Dysfunction
	Therapeutic Strategies
		Removal of Senescent Cells
		Blockade of the Senescent Phenotype
		Controlled Reversal of Cell Senescence
		Cell Senescence as a Problem in Artificial Organs
		Conclusions
	References
Chapter 9: Ageing at Molecular Level: Role of MicroRNAs
	MicroRNAs: Introduction
	Ageing: Molecular Changes and Biomarkers
	Biomarkers of Ageing
	Ageing and Dicer Gene Ablation Studies
	miRNAs Identified for their Role in Ageing of Different Tissues/Organs
		Muscle Ageing and miRNAs
		Bone Ageing and miRNAs
		Heart Ageing and miRNAs
		Skin Ageing and miRNAs
	miRNAs in Neuronal or Brain Ageing
	MiRNAs and Age-Related Cardiac Diseases
	MiRNAs and Age-Related Neurodegenerative Diseases
		Alzheimer´s Disease
		Parkinson´s Disease
		Huntington´s Disease
		Amyotrophic Lateral Sclerosis
	Stem Cell Development and miRNAs
	Stem Cell Pluripotency and Role of miRNAs
	miRNAs and Cardiovascular Differentiation
	Neuronal Differentiation and miRNAs
	Conclusion
	References
Chapter 10: CircRNA and Ageing
	Introduction
	Biogenesis of circRNA
	Diversity and Types of circRNA
	Expression Patterns of circRNA
	Function of circRNA
	CircRNAs as Regulators of Transcription and Alternative Splicing
	miRNA Sponges
	Modulator of Protein Activity and Expression
	Encoding Functional Proteins
	circRNA in Ageing
	circRNA Transcripts Accumulate During Ageing
	Mechanisms of circRNA Accumulation
	Biological Roles of circRNA in Ageing
	circRNA in Age-Associated Disease
	CircRNA in Neurological Disorders
	CircRNA in Cardiovascular Diseases
	CircRNA in Cancer
	CircRNA in Diabetes
	CircRNA as Biomarkers for Ageing
	Perspectives and Conclusions
	References
11: Extracellular Vesicles and Cellular Ageing
	Intercellular Communication
		Homeostasis and Intercellular Communication
		Intercellular Communication and Ageing
		SASP and Its Pro-inflammatory Components: Age-Related Inflammation
		SASP and Pro-oncogenic Components
		SASP and Paracrine Senescence
		SASP and Autocrine Senescence
	Stem Cells for Regenerative Medicine
		Introduction to Stem Cells
		Importance of Stem Cell Culture Conditions for Clinical Applications
		Stem Cells in Clinical Trials
			Stem Cell Properties Supporting Their Clinical Application
			Stem Cell-Based Therapies: Clinical Trials
				Cardiovascular Diseases
				Neurological Disorders
				Bone and Cartilage Diseases
				Other Pathologies
		Paracrine Effect of Stem Cells
	Extracellular Vesicles as Tools for Intercellular Communication
		EVs: Definition and Classification
		A Brief History of EVs
		EVs Biogenesis
		EV Composition
		EV Internalization and Function
		Isolation Methods
	Extracellular Vesicles in Regenerative Medicine
		Regenerative Medicine: From a Cell-Based to a Cell-free Approach
		EVs in Regenerative Medicine: Sources and Delivery Routes
		Role of EVs in the Ageing Process
		EVs as Gerotherapeutics: Lifespan and Healthspan
		EVs as Gerotherapeutics: Hallmarks of Ageing
		EVs and Age-related Diseases
			Cardiovascular Diseases
			Neurodegenerative Diseases
			Musculoskeletal Diseases
			Other Diseases
	Concluding Remarks
	References
Chapter 12: Fibrinogen, Coagulation, and Ageing
	Introduction
	Haemostasis
	Haemostatic Changes with Age
	Platelet Function
	Anti-aggregators of Platelets
	Platelet-Endothelial-White Blood Cell Immuno-pathological Interactions
	Platelet Activity and Cardiovascular Disease
	Platelet Changes with Age
	Laboratory Monitoring: Diagnostics, Tests, and Assays
	Laboratory Principles of Tests and Assays for Fibrinogen and Coagulation
	Anticoagulation Therapeutics Amongst Older Adults
		Heparin
		Warfarin
	Direct Oral Anticoagulants (DOAC)
	Point-of-Care Testing-International Normalised Ratio (INR)
	Point-of-Care Testing-ROTEM and TEG
	Implications and Future Directions
		The Demands on Blood Supply for an Ageing Population
		Reference Intervals Specific to Older Adults
		COVID-19 and Vaccinations, the Prevalence of Thrombotic Events and Implications for an Older Population with and without Comor...
	Conclusion
	References
Chapter 13: An Insight into Platelets at Older Age: Cellular and Clinical Perspectives
	Introduction
	Qualitative Changes of Platelets at an Older Age
	Hallmarks of Ageing
	Genomic Instability and Epigenetic Alterations
	Loss of Proteostasis
	Mitochondrial Dysfunction
	Altered Intercellular Communication
	Cellular Senescence
	Dysregulated Nutrient Sensing
	Concluding Remarks
	References
Chapter 14: Ageing Skeletal Muscle: The Ubiquitous Muscle Stem Cell
	Stem Cells
		Epigenetics
		Epigenetics and Stem Cell Fate
		Adult Stem Cells and Their Potential
		Skeletal Muscle
		Skeletal Muscle Development-Role of the Stem Cell
		Skeletal Muscle Stem Cells
		Potential of Satellite Cell Models
		Skeletal Muscle Ageing
	Ageing and the Skeletal Muscle Stem Cell
		Ageing, Epigenetics and Skeletal Muscle
	Summary
	References
15: Age-Related Changes in Central Nervous System 5-Hydroxytryptamine Signalling and Its Potential Effects on the Regulation o...
	Overview of 5-HT in the Central Nervous System
		Discovery of 5-HT
		5-HT Distribution in the CNS
		5-HT Synthesis
		5-HT Receptors
	Effects of Age on Serotonergic Signalling
		Effects of Age on Serotonergic Neuronal Number
		Tryptophan Hydroxylase
		Vesicular 5-HT Content
		5-Hydroxytryptamine
		Firing of Serotonergic Neurones
		Release of 5-HT
		Age-Related Changes in 5-HT Clearance from the Synapse
		Effects of Age on Monoamine Oxidase A/B
		Effects of Age on 5-HT Receptors
			5-HT1A Receptors
			5-HT1B Receptors
			5-HT2A Receptors
			5-HT4, 6 and 7 Receptors
	Overview of Effects of Age on Serotonergic Signalling
	Ability of 5-HT to Regulate Lifespan
		Molecular Mechanisms Involved in Sensory Regulation of Lifespan by 5-HT
		Effects of Dead Conspecifics on Lifespan and the Role of 5-HT
		So How Does the Natural Ageing Process and 5-HT Signalling Interact?
	References
16: Systems Biology of Ageing
	Introduction
	Bioinformatics
	Computational Modelling
	Multiscale Models of Ageing
	Conclusion
	References