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: ...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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 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 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....

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...