Chapter
Chapter One: The Mitochondrial Free Radical Theory of Aging
2. Antioxidants and Longevity
3. Mitochondrial ROS Production and Oxidative Damage in mtDNA
4. Longevity and Membrane Fatty Acid Unsaturation
5. DR, mtROS Production, and Oxidative Damage in mtDNA
6. Protein and Methionine Restriction
6.2. Role of mtROS generation and oxidative damage
Chapter Two: Mitochondrial DNA Mutations in Aging
1. Introduction: The Different Faces of the Mitochondrial Theory of Aging
2. Mitochondria, mtDNA, and mtDNA Mutations
2.1. Mitochondrial biology and mtDNA
3. Physiological Outcomes of mtDNA Mutations
3.2. Mitochondrial DNA disease
3.3. Phenotypic threshold
3.4. Recessive and dominant mtDNA mutations
3.5. Dominant lethal mtDNA mutations?
4. Clonal Expansion and Age-Dependent Dynamics of mtDNA Mutations
4.1. Somatic mtDNA mutations need to be clonal to be relevant to cell physiology
4.2. MtDNAs in a cell: A dynamic population of molecules
4.3. Clonal expansion via positive selection
4.4. Clonal expansions via random genetic drift
4.5. Random genetic drift with nonlocal compensatory feedback explains unidirectional expansion of detrimental mutations, ...
5. Effects of Somatic mtDNA Mutations in Aging Tissues
5.4. Interplay of clonal expansion and de novo generation of mtDNA mutations
5.5. The ``Vicious cycle´´
6. Evolutionary Considerations and Interspecies Comparisons
6.1. Is mitochondrial genome too small?
6.2. Are somatic mtDNA mutations under longevity-related selective pressure?
6.3. MtDNA ``mutator´´ mice: Do they confirm or disprove the mtDNA hypothesis of aging?
6.4. Longevity-related sequence traits in mtDNA
6.5. Extended human lifespan and growing contribution of somatic mtDNA mutations
Chapter Three: Mathematical Models of Mitochondrial Aging and Dynamics
2. Fundamentals of Mathematical Modeling
2.1. Reconstructing networks
2.2. Logical models with focus on Boolean modeling
2.3. Continuous modeling-The basics of network dynamics described with ordinary differential equations
2.4. Simplifications specific to metabolic networks-Flux-balance analysis
3. Models of Mitochondrial Aging and Dynamics
3.2. Mitochondrial dynamics
3.3. Accumulation of deletion mutants
4. Conclusions and Perspectives
Chapter Four: Mitochondrial Dynamics in Aging and Disease
2. Mitochondrial Trafficking and Localization Within Cells
2.1. Localization of mitochondria within cells
2.2. Trafficking of mitochondria within cells
2.2.1. Neurodegenerative disorders related to impaired mitochondrial trafficking
2.3. How do mitochondria associate with energy requiring structures within cells?
3. Fusion and Fission Regulate Mitochondrial Size and Functionality
3.1. The fusion and fission machinery and its control
3.2. The physiological significance of fusion and fission
3.2.1. Ubiquitous fusion and fission
3.2.2. Fusion and fission as related to aging
3.2.3. Fusion and fission as related to apoptosis and neuronal degeneration
3.2.4. Linking trafficking, fusion and fission
3.2.5. The role of fusion and fission for mtDNA integrity
4. Dynamics of Proteins Within Mitochondrial Membranes and the Matrix
Chapter Five: The Retrograde Response: A Conserved Compensatory Reaction to Damage from Within and from Without
2. The Retrograde Signaling Pathway
3. Consequences of Retrograde Signaling
4. Other Retrograde Responses in Yeast
5. The Retrograde Response and Cell Quality Control
6. Retrograde Response in Other Organisms
7. Evolution of the Retrograde Response as a Cytoprotective Mechanism
Chapter Six: Mitochondrial Acetylation and Genetic Models of Parkinson´s Disease
1. Introduction: Longevity Modulation by Nutrient and Bioenergetic Pathways
2. The Central Role of Sirtuins
3. Mitochondrial Deacetylation Effects on Oxidative Stress and Cancer
5. Mitochondrial Clearance in PD Patient Cells
6. Available Genetic Animal Models for PD-Associated Mitochondrial Pathology
7. Preliminary Findings on Mitochondrial Acetylation in Our PD Mouse Model
Chapter Seven: Mitochondrial Dysfunction: Cause and Consequence of Alzheimer´s Disease
1. Brain Aging: The Role of OXPHOS and ROS
2. Mitochondrial Dysfunction in Alzheimer´s Disease
3. Aβ and Tau-A Deleterious Duo for Mitochondrial Function
4. Mitochondrial-Derived ROS Induce Aβ Generation-Focus on Complexes I and III
5. Interplay Between Aging and AD: The Balance Between Synergistic Dysfunction and Functional Compensation
6. Pharmacological Strategies to Improve Mitochondrial Function
7. Antioxidants, Flavonoids, Polyphenols, and Ginkgo
10. Conclusion and Further Perspective
Chapter Eight: Mitochondria in Cancer: Why Mitochondria Are a Good Target for Cancer Therapy
1. Mitochondria in Malignant Cells-Culprits or Victims?
2. Mitochondria as Targets for Anticancer Therapy
3. Conclusions and Perspectives
Chapter Nine: Estrogen and Mitochondria Function in Cardiorenal Metabolic Syndrome
2.1. Mitochondria structure and function
2.2. Risk factors in mitochondria function
2.3. Mitochondria dysfunction in CRS
3. Estrogen and Mitochondrial Function
3.1. Estrogen, ERs, and their signaling pathways
3.2. Roles of estrogen in mitochondria function
4. Abnormalities in Estrogen Signaling Promotes Development of the CRS
4.1. Estrogen and ERs in CVD
4.2. Estrogen regulates glucose homeostasis and IR
4.3. Estrogen regulates lipogenesis and lipolysis
4.4. Estrogen regulates inflammatory responses
Chapter Ten: Advances in Development of Rechargeable Mitochondrial Antioxidants
3. Age-Dependent Disorders
6. Neurodegenerative Diseases
8. Novel Mitochondrial Antioxidants