The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki

Recommendations

Info

114 The Mitochondrial Free Radical Theory of Aging 37. Nourooz-Zadeh J, Tajaddini-Sarmadi J, Ling KL et al. Low-density lipoprotein is the major carrier of lipid hydroperoxides in plasma. Relevance to determination of total plasma lipid hydroperoxide concentrations. Biochem J 1996; 313:781-786. 38. Cortopassi GA, Shibata D, Soong NW et al. A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues. Proc Natl Acad Sci USA 1992; 89:7370-7374. 39. Brierley EJ, Johnson MA, James OF et al. Effects of physical activity and age on mitochondrial function. QJM 1996; 89:251-258. 40. Carlson BM, Faulkner JA. Muscle transplantation between young and old rats: Age of host determines recovery. Am J Physiol 1989; 256:C1262-C1266. 41. Pearson AGE. Histochemistry: theoretical and applied. 2nd ed. London: Churchill, 1961. 42. Morel DW, DiCorleto PE, Chisolm GM. Endothelial and smooth muscle cells alter low density lipoprotein in vitro by free radical oxidation. Arteriosclerosis 1984; 4:357-364. 43. Steinbrecher UP. Role of superoxide in endothelial-cell modification of low-density lipoproteins. Biochim Biophys Acta 1988; 959:20-30. 44. Jessup W, Simpson JA, Dean RT. Does superoxide radical have a role in macrophage-mediated oxidative modification of LDL? Atherosclerosis 1993; 99:107-120. 45. Frei B, England L, Ames BN. Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci USA 1989; 86:6377-6381. 46. Trigatti BL, Gerber GE. A direct role for serum albumin in the cellular uptake of long-chain fatty acids. Biochem J 1995; 308:155-159. 47. a)Brown MS, Goldstein JL. Familial hypercholesterolemia: Defective binding of lipoproteins to cultured fibroblasts associated with impaired regulation of 3-hydroxy-3methylglutaryl coenzyme A reductase activity. Proc Natl Acad Sci USA 1974; 71:788-792. 47. b) Takahashi K, Avissar N, Whitin J et al. Purification and characterization of human plasma glutathione peroxidase: a selenoglycoprotein distinct from the known cellular enzyme. Arch Biochem Biophys 1987; 256:677-686. 48. Esworthy RS, Chu FF, Geiger P et al. Reactivity of plasma glutathione peroxidase with hydroperoxide substrates and glutathione. Arch Biochem Biophys 1993; 307:29-34. 49. Mahley RW, Innerarity TL, Pitas RE et al. Inhibition of lipoprotein binding to cell surface receptors of fibroblasts following selective modification of arginyl residues in arginine-rich and B apoproteins. J Biol Chem 1977; 252:7279-7287. 50. Davies MJ, Fu S, Dean RT. Protein hydroperoxides can give rise to reactive free radicals. Biochem J 1995; 305:643-649. 51. de Grey ADNJ. The reductive hotspot hypothesis: an update. Arch Biochem Biophys 2000; 373:295-301.
CHAPTER 10 Frequently-Asked Questions The theory discussed in this book is a particularly easy topic on which to give seminars: not so much because it is easy to explain, but because it inspires so many lines of thought in the listener, so allowing one to tailor the presentation much more accurately to the target audience than would otherwise be possible. The questions I most often encounter are addressed in this chapter. 10.1. Why Is Carl Lewis Still Alive? Or, to put it less succinctly: “Surely this theory predicts that higher than average energy utilisation would create more LECs, cause more rapid mitochondrial mutation and turnover, and thus cause faster aging? But athletes live quite as long as anyone else—and, indeed, their mtDNA appears to undergo slightly slower damage with age than average.” 1 The big flaw in this logic is that it overlooks the effect of training. It is correct that high energy utilisation would cause high production of LECs. It is also correct, according to the theory set out here, that if we went out today and were a great deal more athletic than usual then we would age more rapidly as a result. Today. But if we were to make a habit of it, there would be a highly relevant adaptive response: we would get fitter. In particular, our respiratory capacity would rise, due to an increase in the number of mitochondria in each fiber of the muscles that we were training. This would mean that the rate of respiration per unit surface area of our inner mitochondrial membranes would be no greater than it was before we began this athletic activity. And it is that, not the total respiration rate, which (according to SOS) determines the rate of turnover of mitochondria. Each individual mitochondrion is no worse off than before. 10.2. Why Haven’t We Evolved Our Mitochondrial DNA Away? It should first be stressed that the continued existence of mitochondrial DNA does not in any way challenge MiFRA, nor even the general idea that mtDNA decline is substantially to blame for aging. This is because there is absolutely no reason why evolution should select for longevity—indeed, ecological factors can just as effectively select the other way (see Section 6.5.2). The survival of the species, not of the individual, is what evolution promotes. Nevertheless, this is a highly interesting question for another reason. As was summarized in Section 2.1, mitochondria originally had many more genes encoded in their own DNA—all those needed for existence as independent prokaryotic cells. Many of these genes were lost because they were redundant with ones in the nucleus, but many had to be retained. Of those, however, most have been transferred into the nucleus. Just 13 protein-coding genes, plus the rRNAs and tRNAs needed to turn their transcripts into protein, remain. 2 The retention of these 13 in the mitochondria is highly “inconvenient,” since it necessitates the retention of masses of mitochondrion-specific machinery, such as a special DNA polymerase and special ribosomal proteins. It is also, admittedly, a lot of trouble to maintain the protein import machinery that transports nuclear-coded proteins into the mitochondrion; but the The Mitochondrial Free Radical Theory of Aging, by Aubrey D.N.J. de Grey. ©1999 R.G. Landes Company.
Page 1 and 2:
COMPANY de Grey The Mitochondrial F
Page 3 and 4:
ISBN: 1-57059-564-X MOLECULAR BIOLO
Page 5 and 6:
7. The Status of Gerontological The
Page 7 and 8:
17. Conclusion: The Role of the Ger
Page 9 and 10:
I cannot overstate my profound grat
Page 11 and 12:
CHAPTER 1 Introduction 1.1. What Is
Page 13 and 14:
Introduction Some may feel that all
Page 15 and 16:
6 The Mitochondrial Free Radical Th
Page 17 and 18:
8 The Mitochondrial Free Radical Th
Page 19 and 20:
10 The Mitochondrial Free Radical T
Page 21 and 22:
Page 23 and 24:
Page 25 and 26:
Page 27 and 28:
18 Fig. 2.7. The respiratory chain.
Page 29 and 30:
Page 31 and 32:
Page 33 and 34:
24 Fig. 2.9. Types of protein impor
Page 35 and 36:
26 Fig. 2.10. Why the DNA bases pai
Page 37 and 38:
Page 39 and 40:
Page 41 and 42:
Page 43 and 44:
CHAPTER 3 An Introduction to Free R
Page 45 and 46:
An Introduction to Free Radicals Ta
Page 47 and 48:
Page 49 and 50:
Page 51 and 52:
An Introduction to Free Radicals Fi
Page 53 and 54:
An Introduction to Free Radicals Re
Page 55 and 56:
Page 57 and 58:
Page 59 and 60:
Page 61 and 62:
Page 63 and 64:
Page 65 and 66:
Page 67 and 68:
Page 69 and 70: 62 The Mitochondrial Free Radical T
Page 71 and 72: CHAPTER 6 History of the Mitochondr
Page 73 and 74: History of the Mitochondrial Free R
Page 91 and 92: CHAPTER 7 The Status of Gerontologi
Page 93 and 94: The Status of Gerontological Theory
Page 95 and 96: The Status of Gerontological Theory
Page 97 and 98: CHAPTER 8 The Search for How Mutant
Page 99 and 100: The Search for How Mutant mtDNA is
Page 107 and 108: CHAPTER 9 The Search for How So Few
Page 109 and 110: The Search for How So Few Anaerobic
Page 119: The Search for How So Few Anaerobic
Page 123 and 124: Frequently-Asked Questions The effe
Page 125 and 126: Frequently-Asked Questions Table 10
Page 127 and 128: Frequently-Asked Questions through
Page 129 and 130: Frequently-Asked Questions has been
Page 131 and 132: Frequently-Asked Questions SOS, sin
Page 133 and 134: Frequently-Asked Questions for almo
Page 135 and 136: Frequently-Asked Questions Fig. 10.
Page 137 and 138: Frequently-Asked Questions Fig. 10.
Page 139 and 140: Frequently-Asked Questions of elect
Page 141 and 142: Frequently-Asked Questions Referenc
Page 143 and 144: Frequently-Asked Questions 45. Clay
Page 145 and 146: CHAPTER 11 A Challenge from Textboo
Page 147 and 148: A Challenge from Textbook Bioenerge
Page 165 and 166: 160 The Mitochondrial Free Radical
Page 171 and 172:
166 The Mitochondrial Free Radical
Page 173 and 174:
Page 175 and 176:
Page 177 and 178:
CHAPTER 14 Ablation of Anaerobic Ce
Page 179 and 180:
Ablation of Anaerobic Cells: Techni
Page 181 and 182:
CHAPTER 15 Transgenic Copies of mtD
Page 183 and 184:
Transgenic Copies of mtDNA: Techniq
Page 185 and 186:
Page 187 and 188:
Page 189 and 190:
Page 191 and 192:
Page 193 and 194:
CHAPTER 16 Prospective Impact on th
Page 195 and 196:
Prospective Impact on the Healthy H
Page 197 and 198:
Prospective Impact on the Healthy H
Page 199 and 200:
Page 201 and 202:
Page 203 and 204:
Index Symbols “~”, 19 A Acetald
Page 205 and 206:
Index Copper 35, 107 see also trans
Page 207 and 208:
Index Heart comparison to man-made
Page 209 and 210:
Index genetic code 23, 115-118, 177
Page 211 and 212:
Index Perhydroxyl radical 41, 122,
Page 213 and 214:
Index protonation see protonation (
Page 215:
MOLECULAR BIOLOGY INTELLIGENCE UNIT
show all

The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?