Models, Molecules and Mechanisms in Biogerontology: Physiological Abnormalities, Diseases and Interventions

Preface
Contents
About the Editor
Part I: Alterations in Nervous System, Genes, Hormones and Immunity During Aging
	1: Neurological Problems of 
the Elderly
		1.1	 Stroke
		1.2	 Dementia
		1.3	 Parkinson’s Disease (PD)
		1.4	 Chronic Subdural Haematoma (CSDH)
		1.5	 Normal Pressure Hydrocephalus (NPH)
		1.6	 Hyponatraemia
		1.7	 Spondylosis
		1.8	 Conclusion
		References
	2: Molecular Marker and Therapeutic Regimen for 
Neurodegenerative Diseases
		2.1	 Introduction
		2.2	 Alzheimer’s Disease
		2.3	 Markers for Alzheimer’s Disease
			2.3.1	 Aβ42
			2.3.2	 Total Tau and€p-Tau
			2.3.3	 MicroRNAs
			2.3.4	 p97/Melanotransferrin (Mtf)
			2.3.5	 Sirtuin
			2.3.6	 Sestrin
			2.3.7	 Plasma Phospholipids
			2.3.8	 5-Lipoxygenase
			2.3.9	 ApoE
		2.4	 Parkinson’s Disease
		2.5	 Markers for Parkinson’s disease
			2.5.1	 α-Synuclein
			2.5.2	 Protein Deglycase (DJ-1)
			2.5.3	 Uric Acid
			2.5.4	 ApoA1
			2.5.5	 MicroRNAs
			2.5.6	 Parkin Gene
		2.6	 Conclusion
		References
	3: Neurodegeneration During Aging: The Role of 
Oxidative Stress Through Epigenetic Modifications
		3.1	 Introduction
		3.2  Aging and 
Oxidative Stress
			3.2.1  Ca2+ Regulation, ROS Generation, and 
DNA Damage
			3.2.2  Mitochondrial Dysfunction and 
Apoptosis
		3.3  Oxidative Stress and 
Epigenetic Modification
		3.4	 Aging and€Antioxidants
			3.4.1	 Antioxidant Enzymes
			3.4.2	 Antioxidant Vitamins
			3.4.3	 Antioxidant Phytochemicals
		3.5	 Conclusion
		References
	4: Polyglucosan Bodies in Aged Brain and Neurodegeneration: Cause or 
Consequence?
		4.1	 Introduction
		4.2	 Polyglucosan Bodies: A€Historical Perspective
		4.3	 Characteristic Features of€Polyglucosan Bodies in€Nervous System
		4.4	 Hypothesis on€the€Origin and€Function of€Corpora Amylacea in€the€Brain
		4.5	 Polyglucosan Bodies in€Nonhuman Brains
		4.6	 Corpora Amylacea in€Neurodegenerative Brains
		4.7	 Neurodegenerative Disorders with€Polyglucosan Bodies Resulting from€Genetic Defects in€the€Glycogen Metabolism
		4.8	 Concluding Remarks
		References
	5: Signaling of Nociceptors and Pain Perception: Impact of 
Age
		5.1	 Introduction
			5.1.1	 Pain Perception
				5.1.1.1	 Nociceptive Signaling
				5.1.1.2	 Supraspinal Processing of€Pain
				5.1.1.3	 Role of€Inflammatory Mediators and€Ion Channels
				5.1.1.4	 Acute and€Chronic Hyperalgesia
			5.1.2	 Effect of€Age on€Pain (Nociceptor Sensitization)
				5.1.2.1	 Somatosensory Changes in€Nociceptors
				5.1.2.2	 Chronic Pain in€Old Age
					5.1.2.2.1	 Diabetic Neuropathy
					5.1.2.2.2	 Osteoarthritis
					5.1.2.2.3	 Postherpetic Neuralgia
					5.1.2.2.4	 Lower Back Pain
				5.1.2.3	 Pain and€Sociopsychological Factors in€Old Age
					5.1.2.3.1	 Pain Modulation by Emotion
				5.1.2.4	 Treatment
					5.1.2.4.1	 Challenges in€Evaluation of€the€Effects of€Age on€Pain Sensitivity
		5.2	 Future Prospects
		References
	6: Association Between Ageing and REM Sleep Loss: Noradrenaline Acting as 
a Mediator
		6.1	 Introduction
		6.2	 Ageing and€Sleep Disturbances
			6.2.1	 REMS and€Ageing
			6.2.2	 Common Symptoms Associated with€Both Ageing and€REMS Loss
		6.3  Ageing and 
Pathophysiological Changes
			6.3.1	 Metabolic Disorders
			6.3.2	 Neurodegenerative Disorders
			6.3.3	 Immunological Diseases
		6.4	 Molecular Changes in€the€Ageing Brain
			6.4.1	 Changes in€Gene Expression
			6.4.2	 Age-Related Epigenetic Changes
			6.4.3	 REMS Loss-Associated Molecular and€Epigenetic Changes in€the€Brain
		6.5	 Age-Related Changes in€NA Levels
			6.5.1	 REMS Loss-Associated Effects Could be€Induced by€Elevated NA in€the€Brain
		6.6	 Conclusion and€Working Hypothesis/Model
		References
	7: Age-Related Changes in the Human Retina: A Role for 
Oxidative Stress
		7.1	 Introduction
		7.2  Aging Changes in the 
Human Retina
			7.2.1	 The Retinal Pigment Epithelium
			7.2.2	 Photoreceptor Cells
			7.2.3	 Photoreceptor Synaptic Changes
			7.2.4	 Age-Related Loss of€Photoreceptor Cells
			7.2.5	 Age-Related Changes in€the€Inner Retinal Layers
		7.3  Localization of Biomarkers of Oxidative Stress in 
Human Retina
			7.3.1	 4-Hydroxy-2-Nonenal (HNE)
			7.3.2	 Nitrotyrosine
		7.4	 Immunohistochemical Localization of€Antioxidant Enzymes in€the€Human Retina
		7.5	 Oxidative Stress in€the€Aging Human Retina
		7.6	 Oxidative Stress Responses in€the€Aging Human Retina
		7.7	 Does Oxidative Stress Affect Vision in€the€Elderly Humans?
		7.8	 Future Research
		References
	8: Aging: Influence on€Duchenne Muscular Dystrophy (DMD) and€Becker Muscular Dystrophy (BMD)
		8.1	 Introduction
		8.2	 DMD and€BMD
			8.2.1	 Incidence
			8.2.2	 Cause
			8.2.3	 Clinical Symptoms and€Signs
			8.2.4	 Diagnosis
				8.2.4.1	 EMG (Electromyography)
				8.2.4.2	 Blood Enzyme Estimation
				8.2.4.3	 Gene Mutation Analysis
				8.2.4.4	 Histopathological- and€Immunohistochemical-Based Examination
				8.2.4.5	 Metabolomics-Based Possible Diagnostic Approach
			8.2.5	 Aging
				8.2.5.1	 Clinical Symptoms and€Disease Progression
				8.2.5.2	 Pattern of€Muscle Power in€DMD and€BMD
				8.2.5.3	 Cardiac Involvement in€DMD and€BMD
				8.2.5.4	 Central Nervous System Involvement in€DMD and€BMD
				8.2.5.5	 Biochemical Abnormalities in€Body Fluids in€Patients with€DMD and€BMD
				8.2.5.6	 Morphological Abnormalities in€Patients with€DMD and€BMD
				8.2.5.7	 Medication [Corticosteroids (Prednisone and€Deflazacort)] in€DMD and€BMD
				8.2.5.8	 Oxidative Stress in€DMD and€BMD
		References
	9: Mitophagy, Diseases, and€Aging
		9.1	 Introduction
		9.2	 Causes of€Aging
			9.2.1	 Mitochondrial DNA Mutation
			9.2.2	 Oxidative Stress and€ROS
			9.2.3	 Epigenetic Regulation
		9.3	 Mitophagy
		9.4	 Mitophagy and€Aging
		9.5	 Mitophagy and€Senescence
		9.6	 Reversal of€Aging Through€Therapeutic Intervention of€Mitophagy
		9.7	 Conclusion and€Future Prospective
		References
	10: Genetics, Ageing and€Human Health
		10.1	 Introduction
		10.2	 Ageing as€a€Clinical Indication
		10.3	 Alzheimer’s Disease
			10.3.1	 Genetic Basis of Alzheimer’s Disease
			10.3.2	 Early-Onset Alzheimer’s Disease
			10.3.3	 Late-Onset Alzheimer’s Disease
		10.4	 Parkinson Disease (PD)
			10.4.1	 Genetic Heterogeneity of€PD.
		10.5	 Osteoarthritis
			10.5.1	 Genetic Basis
		10.6	 Huntington Disease
		10.7	 Cardiovascular Disease
			10.7.1	 Genetic Basis of€Idiopathic Ventricular Fibrillation (IVF)
		10.8	 Adult Polyglucosan Body Disease
			10.8.1	 Clinical Feature
			10.8.2	 Molecular Genetics
		References
	11: Genetic Syndromes and€Aging
		11.1	 Background
		11.2	 Premature Aging and€Genetic Syndromes
			11.2.1	 Hutchinson-Gilford Progeria Syndrome (HGPS)
			11.2.2	 Cockayne Syndrome (CS)
			11.2.3	 Down Syndrome (DS)
			11.2.4	 Werner Syndrome (WS)
			11.2.5	 Ataxia-Telangiectasia (AT)
			11.2.6	 Bloom Syndrome (BS)
			11.2.7	 Fanconi Anemia (FA)
			11.2.8	 Xeroderma Pigmentosum (XP)
			11.2.9	 Rothmund-Thomson Syndrome (RTS)
		11.3	 Recapitulation of€Features of€Aging in€Syndromes and€Aging Theories
		11.4	 Conclusion
		References
	12: Role of€Stress and€Hormones of€the€Hypothalamic-Pituitary-Adrenal (HPA) Axis in€Aging
		12.1	 Introduction
		12.2	 The Hypothalamic-Pituitary (HP) Axis
		12.3	 The Hypothalamic-Pituitary-Adrenal (HPA) Axis
		12.4	 Cortisol
		12.5	 Dehydroepiandrosterone (DHEA) and€Its Sulfate (DHEAS)
		12.6	 The HPA Axis Dysregulation in€Chronic Stress and€Aging
		12.7	 Cortisol Dysregulation
			12.7.1	 Animal Studies
			12.7.2	 Human Studies
		12.8	 DHEA/DHEAS Dysregulation
		12.9	 Conclusion
		References
	13: Sex Steroids, Cognate Receptors, and€Aging
		13.1	 Introduction
		13.2	 Steroid Hormone Biosynthesis
		13.3	 Sex Steroid Receptors: Their Nuclear Localization
		13.4	 Androgen Receptor (AR), Androgen Action, and€Aging
			13.4.1	 AR Activity in€the€Liver and€Its Age-Dependent Regulation
			13.4.2	 Androgen Dependence of€Normal Prostate and€Prostatic Diseases of€Old Age
		13.5	 Androgen, Estrogen, and€Aging
			13.5.1	 Testosterone in€Aging Males
			13.5.2	 Estrogen and€Female Aging
		13.6	 Influence of€Sex Steroids on€Diseases Prevalent in€Aging
			13.6.1	 Osteoporosis
			13.6.2	 Sex Steroids and€Sarcopenia (Muscle Loss)
			13.6.3	 Sex Steroids, Cardiovascular Diseases, and€Aging
			13.6.4	 Sex Hormones and€Neuroprotection
			13.6.5	 Testosterone and€Erectile Dysfunction
			13.6.6	 Estrogen and€Skin Aging
		13.7	 Hormone Replacement Therapy (HRT) and€Aging
		13.8	 Discussion and€Conclusion
		References
	14: Immunosenescence, Inflammaging, and€Their Implications for€Cancer and€Anemia
		14.1	 Introduction
		14.2	 Aging and€Innate Immunity
		14.3	 Age-Related Changes in€the€Innate Immune Cells
			14.3.1	 Natural Killer Cells in€Aging
			14.3.2	 Monocytes in€Aging
			14.3.3	 Dendritic Cells in€Aging
			14.3.4	 Macrophages in€Aging
			14.3.5	 Neutrophils in€Aging
			14.3.6	 Mast Cells in€Aging
		14.4	 Aging and€Adaptive Immunity
			14.4.1	 T Lymphocytes in€Aging
			14.4.2	 B Lymphocytes in€Aging
		14.5	 Inflammation: An€Important Component of€Innate Immunity
		14.6	 Chronic Inflammation
		14.7	 Inflammaging
		14.8	 Mast Cells and€Inflammaging
		14.9	 Oxidative Stress: Direct Correlation with€Anemia and€Inflammaging
		14.10	 Critical Interplay of€Mast Cells in€Anemia
		14.11	 Aging and€Cancer
		14.12	 Future Insight for€Inflammaging and€Disease Management: A€Concluding Remark
		References
	15: Bone Marrow Stem Cells, Aging, and€Age-Related Diseases
		15.1	 Introduction
			15.1.1	 Bone Marrow
			15.1.2	 Cellular Components of€Bone Marrow
				15.1.2.1	 Bone Marrow Stem Cells and€Function and€Aging
					15.1.2.1.1	 Hematopoietic Stem Cells (HSCs) and€Functions
					15.1.2.1.2	 Hematopoietic Stem Cells (HSCs) and€Aging
					15.1.2.1.3	 Mesenchymal Stem Cells and€Functions
					15.1.2.1.4	 Mesenchymal Stem Cells and€Aging
					15.1.2.1.5	 Multipotent Adult Progenitor Cells (MAPCs), Functions, and€Aging
					15.1.2.1.6	 Bone Marrow Stromal Cells: Functions and€Aging
					15.1.2.1.7	 Bone Marrow Niche and€Functions
					15.1.2.1.8	 Bone Marrow and€Aging
			15.1.3	 Soluble Components of€Bone Marrow
		15.2	 Aging
			15.2.1	 Axis or Theory of€Aging with€Respect to€Bone Marrow/Stem Cells
				15.2.1.1	 Stem Cell Theory of€Aging
				15.2.1.2	 Gene Expression Changes
				15.2.1.3	 Epigenetic Mechanisms
				15.2.1.4	 ROS Affects HSC Aging
				15.2.1.5	 Metabolic Pathways in€Aging
				15.2.1.6	 Telomeres and€Aging
		15.3	 Aging- and€Bone Marrow-Related Diseases
			15.3.1	 Cancer
			15.3.2	 Altered B Lymphopoiesis
			15.3.3	 Osteoporosis
			15.3.4	 Age-Related Macular Degeneration (AMD)
		15.4	 Bone Marrow Therapy in€Age-Related Diseases
			15.4.1	 Bone Marrow Transplantation
				15.4.1.1	 Type-2 Diabetes Mellitus (T2DM)
				15.4.1.2	 Osteoporosis
				15.4.1.3	 Alzheimer’s Disease (AD)
				15.4.1.4	 Bone Marrow Stem Cell Therapy for€AMD
		15.5	 Conclusion
		References
Part II: Interventions for Healthy Aging
	16: Infantile Radiation and€Aging Stresses: Effects of€Calorie and€Dietary Restrictions
		16.1	 Introduction
		16.2	 Effect of€Adult-Onset CR on€the€Life€Span and€Lifetime Cancer Risk After€Early-Life Exposure to€Ionizing Radiation
			16.2.1	 Animal Models
			16.2.2	 Cancer Prevention Effects of€Adult-Onset CR on€Childhood Exposure to€Radiation
			16.2.3	 Mechanism of€CR Effect on€Cancer Prevention
		16.3	 Effect of€CR/DR Initiated During€Old Age on€Life€Span and€Selected Aging Parameters
			16.3.1	 Effect of€CR/DR Initiated from€Old Age on€Life€Span of€Animals
			16.3.2	 Effect of€CR/DR Initiated from€Old Age on€Parameters Known to€Change with€Age
		References
	17: Mechanisms and€Late-Life Intervention of€Aging
		17.1	 Introduction
			17.1.1	 Definition and€Hallmarks of€Aging
			17.1.2	 Animal Models of€Human Physiological Aging
			17.1.3	 Physiological vs. Pathological Models of€Aging
			17.1.4	 Private and€Public Mechanisms of€Aging
		17.2	 Intervention in€Aging
			17.2.1	 A Note on€Pharmacological Intervention by€Defined Chemicals
			17.2.2	 Intervention by Dietary or Caloric Restriction
			17.2.3	 Regular Exercise
		17.3	 Concluding Notes and€Perspectives
		References
	18: Healthy Ageing and€Cancer in€Humans
		18.1	 Introduction
		18.2	 What Is the€Purpose of€Human Life?
		18.3	 Environmental Exposure and€Human Diseases Including€Cancer
		18.4	 Genomic Alterations and€Neoplastic Transformation
		18.5	 Cancer Is Not a€New Disease
		18.6	 Lifestyle and€Cancer
		18.7	 Modern (Allopathy) and€Ancient (Ayurveda, Yoga, and€Pranayama) Modalities in€Cancer Management
		18.8	 Evidence-Based Cancer Prevention
		18.9	 Frequently Asked Biological Questions About Cancer
		18.10	 More Females in€Animal and€Cell Line Are Needed in€Biomedical Research
		18.11	 Cancer and€Ageing-Related Unanswered Questions
		18.12	 Conclusions
		References
	19: Nutrition for€Elderly
		19.1	 Introduction
		19.2	 WHO Guidelines
		19.3	 Elderly Women Health
		19.4	 Common Ailments in€the€Elderly
			19.4.1	 Food-Related Factors and€Ageing
		19.5	 Dietary Guidelines
			19.5.1	 Meal Planning
		19.6	 Body Weight and€Metabolism
		19.7	 Can Nutrition Modulate the€Ageing Process?
		19.8	 Dietary Restriction
		References
	20: Care of€Older Persons in€India: Scope of€Policy and€Technology Tools
		20.1	 Introduction
		20.2	 State Interventions
		20.3	 Policies and€Programs on€Older Persons in€India
			20.3.1	 National Policy on€Older Persons
			20.3.2	 National Program of€Healthcare for€the€Elderly
		20.4	 Social Welfare System Functioning in€Supporting Older Persons
		20.5	 Assessing the€Problem: National Sample Surveys
		20.6	 Home Care and€Long-Term Care
		20.7	 Application of€Technology in€Home Care/Long-Term Care
		20.8	 Future of€Health and€Long-Term Care of€Older Persons in€India
		References