The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki

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The Mitochondrial Free Radical Theory of Aging
of those mechanisms. From this is inferred, among other things, that the design of higher
animals is incompatible with indefinite survival, and therefore that “the goal of extending
human lifespan...—at least in extreme form—is an illusion.” 2 This logic is, in my view,
unsound. My difficulty with it is that it assumes that the discovery of these unknown finer
details will not markedly increase our ability to improve our design. That assumption is
based on an over-zealous reaction to the over-selling that I mentioned above. It is illogical
to assume that if a process influences the rate of aging then it is the main influence; but it is
equally illogical to assume that, if many processes have some influence, then none has a
dominant influence.* And if some process does indeed have a dominant influence on the
rates of all the otherwise unavoidable changes that comprise aging, and discovery of its finer
details were to proceed to the point where (with the medical technology of the time) it
could be largely subverted, our lifespan potential would indeed be greatly increased.
(It would not be rendered indefinite by that single advance, but the practical difference
between the two is rather slight, as will be discussed in Chapter 17.) These are big “ifs,” to be
sure.
My third reason ties the others together and explains why I work in theoretical
gerontology. I maintain that the framework presented here is a true theory of aging, avoiding
both of the logical shortcomings described above. I do not claim that this hypothesis is
proven, but I will explain in the next few chapters that it is now substantially more detailed
and experimentally supported than the very incomplete hypotheses with which gerontology
has hitherto struggled. This is double-edged, though: the very fact that MiFRA is now so
detailed means that it is virtually certain to be partly wrong, and to be easily demonstrated
to be so. I regard this as a good thing, because falsification is the basis of scientific progress;
moreover, when one component of a coherent theoretical framework is falsified, the
remainder of that framework serves as a valuable foundation for identifying a replacement.
Though it risks sounding over-glib, I like to say that I prefer to be wrong nine times out of
ten than zero times out of zero.
7.2. What Causes What?
In case Chapter 6 gave the impression that, by 1995, the case was closed (or, at least,
closing) that mtDNA decline was the predominant culprit in mammalian aging, I will now
return to the shortcomings of that view. In common with some of the other popular lines of
thought, it was relatively unchallenged by the facts; its difficulties lay in what it did not say.
It contained two large and serious gaps—one intracellular, one intercellular—which
undermined the precept that mtDNA mutations are the main originating cause of human
aging.
It is perfectly normal, of course, for a developing hypothesis to contain gaps—sometimes,
large gaps. This is not necessarily a huge barrier to acceptance of the hypothesis as being
“very probably on the right lines.” But in aging it matters a great deal, because of the massive
interdependence of degenerative processes that was discussed in Chapter 5. Virtually any of
them can plausibly be proposed as the cause and/or the effect of any other. This is the main
reason why so many theorists have fallen foul of the “over-selling” problem that I mentioned
in Section 7.1: in order to avoid it one must find a way out of this pervasive, mutual causality.
In particular, MiFRA was still vulnerable to the complaint that all the observed characteristics
of mtDNA decline might also result if it were only a downstream phenomenon, driven by
oxidative stress that was predominantly generated by some other means.
* This is especially so in view of the clear evidence that these various processes act synergistically to accelerate
each other, as was discussed in Section 5.6.