The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki

Prospective Impact on the Healthy Human Lifespan
smaller structures: mice, for example, can fully and perfectly regrow the tip of a toe so long
as they retain the stem cells at the base of the claw, 10 and a comparable effect has been
reported in young children. 11
16.2. Is MiFRA a Theory of Aging?
One can also seek to challenge a theory of aging that proposes a specific mechanism, as
noted in Section 7.1, on the grounds of insufficient verification of the mechanism’s dominant
role. I believe that, while more testing of MiFRA is undoubtedly warranted, it is too well
supported by the evidence for its conclusions to be legitimately ignored—especially since,
as they relate to extension of healthy lifespan, those conclusions are so dramatic. Taken
down to its bare bones, MiFRA can be summed up in four statements:
1. SOS is the main cause of the accumulation of non-dividing cells with no OXPHOS
function.
2. That is the main cause of the progressive increase of oxidative stress throughout the
body.
3. That is the main cause of the decline of cellular and extracellular maintenance.
4. That is the main determinant of the rates of all currently immutable aspects of
human aging.
If all these four statements are true, then abolition of step 1 (by the treatment described
in Chapter 15, or in some other way), or of step 2 (e.g. by the treatment described in Chapter
14) would slow down all aspects of human aging by a large factor. How sure can we be that
they are true? Let us consider them in turn.
Statement 1 is very strongly supported by current evidence, as discussed in Chapter 8.
Furthermore, the details of the SOS mechanism are sufficiently precise that, I believe, any
experiment which showed SOS to be incorrect would almost certainly also show how it
could be corrected—in other words, it would at once give us a replacement theory which
was closer to being correct. More importantly, however, it does not matter exactly how
OXPHOS fails in these cells: what matters is that this failure may realistically be avertable by
gene therapy, as discussed in Chapter 15.
Statement 3 is also very strongly supported. All maintenance processes in the body are
mediated by proteins, which can be generated “at will” by all cells. The only requirements
for indefinite retention of those maintenance processes, therefore, are:
a. The supply of sufficient nutrients and oxygen to make the ATP to drive maintenance.
This is not limited—at least, not by our biology.
b. The genetic ability to generate this ATP. As observed earlier, this remains intact in at
least 99% of cells—and would be so in virtually 100% of cells if the therapy described
in Chapter 15 were achieved.
c. The retention of wild-type, and properly regulated, genes encoding the proteins
involved in maintenance (which are all nuclear-coded). The rate at which genes
become mutant has been computed in various ways, such as from the rate of
incidence of cancer, and is thus known to be far too low to account for more than a
tiny fraction of the observed rate of decline of maintenance. 12 There is likewise, as
yet, no evidence to support the theory that misregulation (for example,
dysdifferentiation) 13 occurs in vivo to an extent that could significantly influence
the rate of aging.
d. The absence of an increase in the average rate of occurrence of damage requiring
repair. Such an increase necessarily impacts the efficacy of maintenance. But damage
can only arise (if we exclude macroscopic physical injury or exogenous toxins) from
endogenous chemical damage; and the only endogenous toxins—accumulating
sources of this damage—are pro-oxidants. Thus, accelerating damage from internal
causes can result only from increasing oxidative stress.
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