The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki

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The Mitochondrial Free Radical Theory of Aging
5.6.3. Positive Feedback
One of the major lines of thought that will be discussed in the next chapter is known as
the “vicious cycle theory.” This name is rather unfortunate, because the theory in question
was a very specific proposal for the mechanism of age-related mitochondrial decline, whereas
“vicious cycle” is an extremely general term describing any system which undesirably
accelerates its own rate of change—that is, which exhibits positive feedback. The vicious
cycle theory did indeed hypothesise such a system, but many other systems are also vicious
cycles.
More to the point, many aspects of aging can be so described. A prominent example is
atherosclerosis, in which the lesion grows increasingly rapidly as the surrounding tissue
resorts to ever more drastic measures to control it. At the molecular level, there is an interplay
between oxidation and glycation, 40 which makes glycation harmful over and above its effects
on unrecycled tissues (discussed in Section 5.3). For example, LDL can undergo glycation;
this does not of itself make LDL toxic, but it does make it more prone to undergo
oxidation and thereby become toxic, with the result that diabetics are unusually prone to
atherosclerosis. 41 This interplay also goes the other way—oxidation exacerbates the
deleterious effects of glycation, because the irreversible cross-links (such as pentosidine)
that were discussed in Section 5.3 require an oxidation reaction following the glycation
process. For this reason, pentosidine and its relatives are sometimes called glycoxidation
products. 42 This dependency may help explain why birds can sustain such high blood
glucose (see Section 6.5.6); biochemical investigation of glycation in birds has so far
been restricted to relatively short-lived poultry, however. 43
5.7. An Interim Conclusion: The Overinterpretable Pleiotropy
of Human Aging
5.7.1. Biochemical Pleiotropy
This chapter has reviewed only rather superficially the major changes that occur in our
bodies as we age, but it suffices to remind us, if we needed reminding, that they are
intimidatingly many and varied. Perhaps it is that, more than any other characteristic, which
has caused gerontology to be much less popular as a field of study than non-biologists might
expect it to be.
It should also be apparent, however, that the more deeply one explores these many
processes, the more they reveal themselves to have in common. This commonality is most
evident not in the mechanisms that initiate these processes, but rather in the
microenvironmental features that determine the rate of that initiation. Oxidative stress
has a strong claim to being the main accelerating factor for all of them. Moreover, the root
causes of increasing oxidative stress cannot be all that numerous, since they are restricted
to the unrecycled materials listed in Section 5.6.1. And even among those, there is no reason
to suppose that all make the same contribution; equally possible, a priori, would be that
one is the primary culprit.
There is thus a very real possibility that the continued exploration of aging will follow
very much the same pattern as did the exploration of cells' energy utilisation. It was appreciated
for many decades that energy was used in a huge number of biological processes, and
similarly that it could be extracted from a huge number of different nutrients. Now, however,
we know that the link between energy extraction and energy utilisation involves just
one molecule, ATP. Lonely electrons are shaping up to fill the role in aging that ATP does in
metabolism.