The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki

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.