The Mitochondrial Free Radical Theory of Aging
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Edited By:Aubrey D.N.J. de GreyUniversity of Cambridge ISBN: 978-1-57059-564-6 Published: 1999-12-01 This book may be purchased as an eBook (pdf) for $99, or individual chapters (pdf) may be purchased from the list below for $19. |
The vast complexity of organismal degeneration with age has too often intimidated gerontologists into over-cautious interpretation of their results. Therefore, theories of mammalian aging have been too open and preliminary to underpin the design of medical interventions. This book breaks new ground in the effort to overcome that inertia, by providing a highly detailed and experimentally well-founded model of mammalian aging, together with analysis of the ways in which that model may be exploited to influence the rate of aging. It will benefit biologists, clinicians and the scientifically-minded laypersons alike, by giving a robust conceptual structure to compare with ongoing experimental and medical findings.
Chapters available from this book
Conclusion: The Role of the Gerontologist Today
Aubrey D.N.J. de Grey
Firstly: not just because I believe that what I have written is true—that would not have been sufficient. This is certainly not the first book ever published which suggests the significant possibility of great increases in healthy human lifespan in the foreseeable future, and the...
Prospective Impact on the Healthy Human Lifespan
Aubrey D.N.J. de Grey
The message of the previous two chapters is that we have a realistic chance of achieving, in only a few decades, a degree of control over the rate of human aging which far exceeds anything that has hitherto seemed feasible. Since that conclusion is rather dramatic, I will use this penult...
Transgenic Copies of mtDNA: Techniques and Hurdles
Aubrey D.N.J. de Grey
The conclusion of the previous chapter is somewhat ambivalent: I believe that selective ablation of affected cells is a concept worthy of consideration and research, but may in the end prove unable to retard systemic mtDNA decline all that much. Therefore, I feel that only one approac...
Ablation of Anaerobic Cells: Techniques and Hurdles
Aubrey D.N.J. de Grey
The death of cells is not always something that the body seeks to avoid. There are two major pathways involved in cell death, called necrosis and apoptosis; apoptosis is the one that will be highlighted here, because it has features which appear quite readily amenable to recruitment f...
Prospects for Intervention
Aubrey D.N.J. de Grey
The retardation or reversal of aging has been a desire of mankind for as long as we can trace, but biologists have not worked particularly hard to achieve it. One reason for this—a very poor one, in my view—is that it is clearly a very hard problem, and therefore one on which p...
Some Testable Predictions of MiFRA
Aubrey D.N.J. de Grey
It has often been observed that gerontology is heavy on data but light on theory. A consequence of this is that, when a theory is propounded which fits the data already available, it may be unusually difficult to identify experiments to test it: the problem is that so many of the experim...
A Challenge from Textbook Bioenergetics and Free Radical Chemistry
Aubrey D.N.J. de Grey
This chapter might, logically, have been included as a section of the previous chapter, since it addresses a challenge to SOS. A thorough response to this particular challenge, however, is necessarily chapter-sized. The challenge is as follows:
"SOS states that mitochondria w...
Frequently - Asked Questions
Aubrey D.N.J. de Grey
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...
The Search for How So Few Anaerobic Cells Cause So Much Oxidative Stress
Aubrey D.N.J. de Grey
The apparently low level of mutant mtDNA even in very elderly individuals was perhaps the most powerful argument, in 1995, against the idea that mtDNA decline is central to aging. This was stressed in a number of articles at the time; a representative study from 19921 drew par...
The Search for How Mutant mtDNA is Amplified
Aubrey D.N.J. de Grey
This gap in the mitochondrial free radical theory was a particularly inviting challenge to a newcomer in the field. Superficially, it seemed that all the information was available to lead rapidly to a detailed mechanism for how mutant mitochondria out–competed wild–type ones; b...
The Status of Gerontological Theory in 1995
Aubrey D.N.J. de Grey
The central motivation of this chapter is a fact that may surprise, if not appall, non–biologists: that theoretical biology has a bad name. Theoretical gerontology, moreover, has a particularly bad name: it is considered to be a magnet for sloppy thinkers with half–baked ideas....
History of the Mitochondrial Free Radical Theory of Aging, 1954-1995
Aubrey D.N.J. de Grey
This chapter, unlike the rest of the book, is structured explicitly as a narrative. Thetheoretical and experimental advances which have given rise to the mitochondrial free radical theory of aging are many and varied, and their contributions to the overall theory are liable to be lost in...
A Descriptive Introduction to Human Aging
Aubrey D.N.J. de Grey
It would be rather strange to present a theory of aging without saying (in more than just that one word) what the theory sets out to explain. Furthermore, a descriptive analysis of the deleterious changes that occur in our bodies late in life offers some very instructive insights into wh...
An Introduction to Metabolism
Aubrey D.N.J. de Grey
When the mitochondrial free radical theory was first conceived, researchers presumed that the process of steady mitochondrial decline was happening independently, and roughly equally, in all cells of a given type. It is now quite certain, however, that the process is very uneven indeed: ...
An Introduction to Free Radicals
Aubrey D.N.J. de Grey
It is most unfortunate that the term "free radical" has become so firmly entrenched in the vocabulary of gerontology, especially in the popular press. The problem is that the meaning which is generally attached to it has several major differences from its strict chemical definition. <...
An Introduction to Mitochondria
Aubrey D.N.J. de Grey
Mitochondria have two main characteristics which, in combination, mark them out among subcellular structures as especially plausible mediators of cellular decline. The first is their absolute indispensability to the cell: they are the intracellular machines that enable us to use oxyge...
Introduction
Aubrey D.N.J. de Grey
It has been said that aging is a difficult thing to define, but in fact a relatively uncontentious definition is possible. Masoro's1 is as good as any:
deteriorative changes with time during postmaturational life that underlie an increasing vulnerability to chal...
