The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki

11. A Challenge from Textbook Bioenergetics and Free
Radical Chemistry ................................................................................. 139
11.1. The Effect of Oxidative Stress
on Non-Mutant Mitochondria ................................................. 139
11.2. Perhydroxyl: The Forgotten Radical ......................................... 139
11.3. Mitchell’s Oversimplification ................................................... 143
12. Some Testable Predictions of MiFRA .................................................. 159
12.1. Some Predictions of SOS ........................................................... 159
12.2. Some Predictions of the Reductive Hotspot Hypothesis......... 160
12.3. Negligible Senescence: Predictions of MiFRA ......................... 161
13. Prospects for Intervention .................................................................... 165
13.1. Some Probably Futile Approaches ............................................ 166
13.2. A Way to Obviate mtDNA ........................................................ 169
13.3. A Way to Destroy Anaerobic Cells ........................................... 170
13.4. Gene Therapy ............................................................................. 170
14. Ablation of Anaerobic Cells: Techniques and Hurdles ....................... 173
14.1. Apoptosis: A Ready-Made Cell Killer ....................................... 173
14.2. Specificity and Frequency of Treatment................................... 173
14.3. Disposal of Dead Cells ............................................................... 174
14.4. Replacement of Dead Cells ....................................................... 174
14.5. Segmental Cell Death ................................................................ 175
15. Transgenic Copies of mtDNA: Techniques and Hurdles ................... 177
15.1. Changes to the Coding Sequences ........................................... 177
15.2. Targeting to Mitochondria....................................................... 177
15.3. Regulation of Expression; Copy Number................................ 178
15.4. Stoichiometry: Interference by Endogenous Wild-Type
mtDNA ...................................................................................... 178
15.5. Interference By Mutant mt-Coded Proteins ........................... 179
15.6. The Inconvenience, But Irrelevance,
of Mitochondrial RNAs ........................................................... 180
15.7. Unfolding, Refolding and Prevention of Folding ................... 180
15.8. Fallacious “Existence Proofs” That This Cannot Work ......... 181
15.9. Import of Very Hydrophobic Proteins .................................... 182
15.10. Hints From Other Organisms .................................................. 182
15.11. Do We Really Need Complex I?............................................... 183
15.12. Cotranslational Import ............................................................ 183
15.13. Semi-Import ............................................................................. 185
15.14. Inteins: A More Coercive Approach ........................................ 186
15.15. More Exotic Technologies ....................................................... 186
16. Prospective Impact on the Healthy Human Lifespan ......................... 189
16.1. Plausibility of Engineered Negligible Senescence .................... 189
16.2. Is MiFRA a Theory of Aging? .................................................... 191