The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki

CONTENTS
1. Introduction .............................................................................................. 1
1.1. What is Aging? .................................................................................. 1
1.2. Subjectivity and Vocabulary ............................................................ 1
1.3. Why Suspect Mitochondria or Free Radicals? ................................ 2
1.4. Tests, Interventions and Consequences .......................................... 2
2. An Introduction to Mitochondria ............................................................ 5
2.1. The Evolutionary Origins of Mitochondria .................................... 5
2.2. Mitochondrial Location and Structure ........................................... 7
2.3. Mitochondrial Function ................................................................. 10
2.4. Mitochondrial DNA, or mtDNA ................................................... 20
3. An Introduction to Free Radicals ........................................................... 35
3.1. Another Terminological Apology: “Pairing” of Electrons ........... 35
3.2. What Do LECs Do?......................................................................... 36
3.3. Where Do LECs Come from In Vivo? ........................................... 36
3.4. The LECs and Related Molecules Relevant to MiFRA ................. 37
3.5. LEC-Related Reactions Relevant to MiFRA .................................. 38
3.6. Fenton Chemistry ........................................................................... 41
3.7. Chains and Branches ...................................................................... 41
3.8. Downstream Products—A Virtually Infinite Variety ................... 44
3.9. Fatty Acid Double Bonds: Fluidity but Oxidisability ................... 44
4. An Introduction to Lipid Metabolism ................................................... 47
4.1. The Major Fat-Related Molecules in Cells: Structural Roles ....... 47
4.2. Synthesis and Transport of Fatty Acids and Cholesterol.............. 50
4.3. Good and Bad LDL ......................................................................... 51
5. A Descriptive Introduction to Human Aging ........................................ 53
5.1. Atherosclerosis ................................................................................ 53
5.2. Cancer ............................................................................................. 54
5.3. Disorganization of Connective Tissue: Skin, Artery,
Eye, Cartilage .................................................................................. 55
5.4. Blindness ......................................................................................... 57
5.5. Other Macroscopic Changes .......................................................... 58
5.6. Feedback, Turnover and Oxidative Stress ..................................... 58
5.7. An Interim Conclusion: The Overinterpretable Pleiotropy
of Human Aging ............................................................................. 60
6. History of the Mitochondrial Free Radical Theory of
Aging, 1954-1995 ..................................................................................... 65
6.1. Precursors of the Mitochondrial Free Radical Theory ................. 65
6.2. The First Mechanistic Idea ............................................................. 65
6.3. Suppressiveness ............................................................................... 66
6.4. Mitochondria as Free Radical Victims .......................................... 66
6.5. Comparisons with Other Species ................................................... 68
6.6. Amplification of Mutant mtDNA; Demise of the Vicious
Cycle Theory ................................................................................... 74