Redox Signaling and Biomarkers in Ageing (Healthy Ageing and Longevity, 15)

Preface
Contents
Editors and Contributors
Part I Redox Dynamics
1 Redox Dynamic Homeostasis and Aging
	1.1 Introduction
	1.2 Lifespan Trajectories
	1.3 General Overview of Redox Homeostasis
	1.4 NAD(P) and NAD(P)H Pairs as Common Redox Denominators
	1.5 Intermediary Metabolism is Linked with Protein Structure Through Kinetically Controlled Processes
	1.6 Spatiotemporal Organization of Redox Signaling
	1.7 Adaptability to Environmental Challenges
	1.8 Conclusive Remarks and Perspectives
	References
2 Reliability and Longevity of Biological Systems: The Free-Radical Redox Timer of Aging
	2.1 Introduction
	2.2 Reliability of Biological Systems: Historical Synopsis and Terminology
	2.3 Longevity and Reliability: Genetics Determinants and Mathematical Theory of Reliability
	2.4 Free-Radical Redox Timer of Aging: Stochastic Realization of the Genetic Program
	2.5 Antioxidant Therapy of Aging: Reliability-Theory Overlook
	2.6 Conclusions and Outlook
	References
3 Disturbances in Redox Homeostasis in the Ageing Brain
	3.1 Introduction
	3.2 Redox Homeostasis in the Brain
		3.2.1 Oxidation of Proteins in the Brain
		3.2.2 Lipid Oxidation in the Brain
	3.3 Redox Alterations and ROS-Mediated Signal Transduction Mechanisms in the Ageing Brain
	3.4 Redox Imbalance in Neurodegenerative Diseases
	3.5 Redox Imbalance and Interventions for Healthy Brain Ageing
		3.5.1 Antioxidants
		3.5.2 Exercise
	3.6 Conclusions
	References
4 Impaired Redox Homeostasis and Cardiovascular Aging
	4.1 Introduction
	4.2 General Mechanisms of Redox Homeostasis
		4.2.1 Reactive Oxygen Species Generation
		4.2.2 Reactive Oxygen Species Scavenging
	4.3 Redox Homeostasis in Cardiovascular System
	4.4 Impaired Redox Homeostasis and Cardiovascular Disease
		4.4.1 Hypertension
		4.4.2 Atherothrombosis
		4.4.3 Atherogenesis
		4.4.4 Cardiomyocytes, Fibroblasts, and Monocytes
		4.4.5 Ischemia–Reperfusion Injury
		4.4.6 Diabetes and Obesity
	4.5 Recent Evidence and Potential Future Therapies
	4.6 Conclusion
	References
5 Redox Homeostasis in Skeletal Muscle Aging
	5.1 Introduction
		5.1.1 ROS Production and Diffusion in Skeletal Muscle
		5.1.2 ROS in the Skeletal Muscle Aging
		5.1.3 ROS-Induced Signaling and Skeletal Muscle Aging
		5.1.4 Physiological Level of ROS in the Skeletal Muscle
		5.1.5 Oxidative Products in the Skeletal Muscle Aging
	5.2 Conclusion
	References
6 Aging and Exercise-Induced Reactive Oxygen Species
	6.1 Introduction
	6.2 Aging, Exercise, and Free Radicals
	6.3 Exercise-Induced Extramitochondrial ROS
	6.4 Exercise-Induced NO
	6.5 Aging, Exercise, and Nrf2 Signaling
	6.6 Exercise-Induced Mitochondrial ROS
	6.7 Aging, Exercise, and PGC1a Signaling
	6.8 Exercise and Antioxidant Defense
	6.9 Conclusion
	References
Part II Redox Signalling and Subcellular Ageing
7 Redox Signalling, Autophagy and Ageing
	7.1 Ageing
		7.1.1 Ageing Process
		7.1.2 Healthy Ageing
		7.1.3 Cellular Ageing
	7.2 Oxidative Stress and Ageing
		7.2.1 Synthesis of ROS
	7.3 Ageing and Mitochondria
		7.3.1 ROS Production in Mitochondria
	7.4 Redox Signalling
		7.4.1 Dual Role of ROS
		7.4.2 Redox Signalling
	7.5 Autophagy
		7.5.1 Lysosomal System in Autophagy
		7.5.2 Autophagy Mechanism
		7.5.3 Types of Autophagy
		7.5.4 Ageing and Autophagy
	7.6 Conclusion
	References
8 Targeting Mitochondria and Redox Dyshomeostasis in Brain Ageing: An Update
	8.1 Introduction
	8.2 Brain Ageing: An Unavoidable Physiological Event
		8.2.1 Mitochondria on the Backstage
		8.2.2 Mitochondria-Redox Status Interplay During Physiological Brain Ageing
		8.2.3 The Importance of Mitochondrial Dynamics in Physiological Brain Ageing
	8.3 Pathological Brain Ageing: The Other Side
		8.3.1 Alzheimer’s Disease
		8.3.2 Parkinson’s Disease
	8.4 Mitochondrial Medicine: Targeting Mitochondria and Redox Imbalance on Brain Ageing, Alzheimer’s and Parkinson’s Diseases
		8.4.1 Diet and Exercise
		8.4.2 Antioxidant-Based Therapies
		8.4.3 Mitochondrial Uncoupling
		8.4.4 Mitochondrial Transplantation
	8.5 Concluding Remarks
	References
9 Importance of CoQ10-dependent Redox Activity in Aging
	9.1 Introduction
	9.2 CoQ is Essential for Mitochondrial Activity
	9.3 Extramitochondrial CoQ10, the Forgotten Key Function
		9.3.1 Antioxidant Activity in Cell Membranes
		9.3.2 Extramitochondrial CoQ Protects Against Apoptosis.
		9.3.3 Membrane CoQ Protects Against Ferroptosis.
		9.3.4 CoQ and the Plasma Membrane Redox System.
	9.4 Prolongevity Effectors Induce CoQ-Dependent Extramitochondrial Activities
	9.5 CoQ Protects Against Plasma LDL Protection.
		9.5.1 Treatment with Statins Decrease CoQ10 Levels in Plasma
		9.5.2 CoQ Levels in Plasma Are Affected by Nutrition
		9.5.3 Plasma CoQ and the Endothelial Function
		9.5.4 CoQ10 Levels in Plasma Are Affected by Aging.
	9.6 Importance of CoQ Homeostasis in Aging
		9.6.1 Mitochondrial Dysfunction as the Main Cause of ROS Increase During Aging
		9.6.2 The Decrease of CoQ10 in Mitochondria: Cause or Consequence of the Dysfunction of Mitochondria
		9.6.3 Do CoQ10 Levels Decrease During Aging in Humans?
	9.7 Concluding Remarks
	References
10 Redox Proteostasis in Subcellular Aging
	10.1 Introduction
	10.2 Mitochondrial Aging and Redox Proteostasis
	10.3 ER Proteome
	10.4 ER-Related Aging and Redox Proteostasis
	10.5 Mitochondria–ER Signaling-Related Communication
	10.6 Mitochondria–Lysosome Signaling-Related Communication
	10.7 Peroxisomal Aging and Redox Proteostasis
	10.8 Concluding Remarks
	References
11 Modulation of Redox and Aging-Related Signaling Pathways and Biomarkers by Naturally Derived Peptides
	11.1 Introduction
	11.2 Antioxidant Activities of Naturally Derived Peptides
		11.2.1 Increase of Survival Under Oxidative Stress by Naturally Derived Peptides
		11.2.2 Enhancement of Antioxidant Defense Systems by Naturally Derived Peptides
		11.2.3 Prolongevity Effects of Antioxidant Peptides
	11.3 Regulation of Redox and Aging-Related Signaling by Antioxidant Peptides
		11.3.1 Regulation of Insulin/IGF-1 Pathway by Antioxidant Peptides
		11.3.2 Regulation of Nrf2/SKN-1 Pathway by Antioxidant Peptides
		11.3.3 Regulation of Other Signaling Pathways by Antioxidant Peptides
	11.4 Conclusion
	References
12 Senolytic Phytocompounds in Redox Signaling
	12.1 Introduction
	12.2 Redox Signaling
	12.3 Mitochondrial Dysfunction in the Context of Cellular Senescence
	12.4 Senolytic Phytocompounds
	12.5 Navitoclax
	12.6 Dasatinib (D) and Quercetin (Q)
	12.7 Fisetin
	12.8 Metformin
	12.9 Spermidine
	12.10 Epigallocatechingallate (EGCG)
	12.11 Rapamycin
	12.12 Senolytics in Cell Signaling Pathways
	12.13 FoxO Pathway
	12.14 p53 Pathway
	12.15 Nrf Pathway
	12.16 NFκB Pathway
	12.17 JAK/STAT Pathway
	12.18 MTOR/PI3K/Akt Pathway
	12.19 The Current Progress of Senolytics
	12.20 Limitations
	12.21 Conclusion
	References
Part III Redox Biomarkers in Age-Related Disorders
13 Impaired Redox Status and Age-Related Neurodegenerative Disorders
	13.1 Introduction
	13.2 Oxidative Stress Biomarkers and Redox Status in the Brain
	13.3 Protein Thiol Modification
	13.4 Impaired Redox Status and Its Consequences Leading to Aging and Age-Related Neurodegenerative Disorders
	13.5 S-nitrosylation and Mitochondrial Dysfunction
	13.6 S-glutathionylation and Neurodegeneration
	13.7 Sulfhydration and Its Impact on Nervous System
	13.8 Glutathione Systems in Neurodegenerative Disorders
	13.9 Oxidative Stress, Mitochondria, and Age-Related Neurodegenerative Diseases
	13.10 Role of Oxidative Stress in Age-Related Neurodegenerative Disorders
		13.10.1 Alzheimer’s Disease (AD)
		13.10.2 Parkinson’s Disease (PD)
		13.10.3 Amyotrophic Lateral Sclerosis (ALS)
		13.10.4 Huntington’s Disease (HD)
	13.11 Conclusion
	References
14 The Effects of Sirtuin Activators on Cerebral White Matter, Redox Biomarkers, and Imaging Findings in Aging Brain
	14.1 Cerebral White Matter and Aging
	14.2 Cerebral White Matter Changes and Findings in Diagnostic Imaging
	14.3 Cerebral White Matter Changes and Redox Biomarkers in Brain Tissue
	14.4 Catalase, Glutathione Peroxidase, and Superoxide Dismutase Levels and Brain White Matter Changes
	14.5 Sirtuins
	14.6 The Effects of SIRT Activators and Senolytics on White Matter Changes and Redox Biomarkers
	14.7 Clinical Trials with Senolytics/SIRT Activators
	14.8 Conclusion
	References
15 Redox Homeostasis in Alzheimer’s Disease
	15.1 Alzheimer\'s Disease
	15.2 The Concept of Homeostasis
	15.3 Redox Homeostasis
	15.4 Redox Dyshomeostasis in AD
	15.5 Main Hypotheses of AD from the Perspective of Redox Homeostasis
		15.5.1 The Amyloid Cascade Hypothesis of AD and Redox Homeostasis
		15.5.2 The Tau Hypothesis of AD and Redox Homeostasis
		15.5.3 The Insulin-Resistant Brain State (IRBS)/Metabolic Dysfunction Hypothesis of AD and Redox Homeostasis
		15.5.4 Other Hypotheses of AD and Redox Homeostasis
	15.6 Redox Dyshomeostasis: A Conjunctive Etiopathogenetic Amplifier of AD
	15.7 Practical Implications and Concluding Remarks
	15.8 Conclusion
	References
16 Aging and Redox Pathways in Diabetes
	16.1 Introduction
	16.2 Hyperglycemia and Oxidative Stress
		16.2.1 Glycolysis Pathway
		16.2.2 Advanced Glycation End-Products Pathway
		16.2.3 Protein Kinase C Activation Pathway
		16.2.4 Hexosamine Pathway
		16.2.5 Polyol (Sorbitol) Pathway
		16.2.6 Insulin Signaling Pathway
		16.2.7 Lipid Peroxidation
	16.3 Diabetes Progression, Complications, and Oxidative Stress
	16.4 Aging and Diabetes
		16.4.1 Mitochondrial Free Radical Theory of Aging
		16.4.2 Aging Beta Cells
	16.5 Diabetes Medication and Oxidative Stress
	References
17 Redox Processes in the Etiopathogenesis of Cerebrovascular Diseases
	17.1 Introduction
	17.2 Risk Factors and Etiology
	17.3 Pathophysiological Mediators
		17.3.1 Neurovascular Unit
		17.3.2 Immune Cells
		17.3.3 Subcellular Mechanisms
	17.4 Future Clinical Implications
		17.4.1 Diagnostics
		17.4.2 Therapeutic Targets
	17.5 Conclusion
	References
18 Redox Status in Age-Related Acute Mesenteric Ischemia
	18.1 Introduction
	18.2 Anatomical Aspects of the Intestinal Blood Flow
		18.2.1 Arterial Circulation
		18.2.2 Arterial Anastomoses and Their Clinical Significance
		18.2.3 Venous Circulation
	18.3 Etiopathogenesis
		18.3.1 Occlusive Mesenteric Ischemia
		18.3.2 Non-occlusive Mesenteric Ischemia
		18.3.3 Age-Related Arterial Alterations, Oxidative Damage, and Mesenteric Ischemia
		18.3.4 Sex, Oxidative Damage and Mesenteric Ischemia
	18.4 Reperfusion Injury and Acute Mesenteric Ischemia
		18.4.1 Effects of Ischemia on Cellular Metabolism
		18.4.2 ROS Formation and Reperfusion
	18.5 Clinical Manifestations of Acute Mesenteric Ischemia
		18.5.1 Clinical Presentation
		18.5.2 Diagnostic Tools for Acute Mesenteric Ischemia
		18.5.3 Surgical Procedures
		18.5.4 Prognosis of Acute Mesenteric Ischemia
		18.5.5 Potential and Promising Treatment Modalities
	18.6 Conclusion
	References
19 Redox Signaling and Biomarkers in the Acute Setting
	19.1 Introduction
	19.2 Redox Biomarkers in Sepsis
	19.3 Redox Biomarkers in Pulmonary Disease
	19.4 Redox Biomarkers in Cardiovascular Disease
	19.5 Redox Biomarkers in Trauma
		19.5.1 Redox Biomarkers in Stroke
	19.6 Conclusion
	References