The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki

190
The Mitochondrial Free Radical Theory of Aging
much larger difference in scale than that—is the correct analogy to consider when assessing
the plausibility of maintenance by biotechnology.
16.1.2. Plausibility of Indefinite Repair and Regeneration
Repair is not easy to distinguish qualitatively from maintenance; if one accepts a
quantitative distinction then perhaps it can be defined as maintenance on a larger scale.
Further along this spectrum are processes which are even more dramatic, and which may
more accurately be termed regeneration.
Certain parts of the human body are never repaired at all, even if the damage they
suffer is very small. Examples are the enamel of teeth and the sensory hair cells of the inner
ear. In order to retain function of such parts indefinitely, we must either develop gene therapy
treatments that revive the regenerative capacity which exists in other vertebrate species but
which we have lost, or else rely on artificial replacements. Enamel is a fantastically durable
material, but some man-made ceramics certainly now equal it. Loss of hearing, due to death
of sensory hair cells, would be very difficult to repair artificially on a cell-by-cell basis, but
the replacement of the entire auditory apparatus has been very effectively achieved with the
development of cochlear implants, whose insertion is now a routine operation in the
treatment of profoundly deaf individuals whose auditory nerve is known to be functional. 2
Another cell type which is purportedly incapable of regeneration in humans is the
neuron. However, this is a shortcoming which does not extend even to all homeotherms,
since some birds are known to renew parts of their brain every year. Moreover, there have
been reports during the past few years of the discovery of neuronal precursor cells in the
brains of both adult mice and adult humans. 3,4 The desirability of a turnover of neurons has
sometimes been questioned on the basis that it would erase parts of our memory; but the
nature of memory—though certainly still very poorly understood—is probably not a case
of individual facts or skills being stored in individual cells or connections: it is likely to be a
great deal more “holographic” than that. Thus there is no reason to think that a very slow
turnover of neurons—which is all that is necessary—would have any effect at all on memories
that are being used enough to be retained in normal life. Explorations of such treatment are
already being considered. 5,6a,6b
The final class of regeneration that must be considered is that of highly complex
structures. This includes large-scale reconstruction, such as of limbs, and also small-scale
but highly intricate reconstruction, such as of the connections between the individual neurons
of a severed optic nerve. Both are classic cases of repair which is far beyond our natural
capacity, and is also quite impossible with present surgical techniques; the reconstruction of
a complex three-dimensional structure such as a limb is a technology which, in many people’s
eyes, is permanently in the realms of science fiction. Again, however, there is a remarkable
capacity for such regeneration in certain other vertebrates—the best-studied examples are
amphibians, such as Xenopus for the optic nerve 7 and axolotls for the limb. 8 I suspect that
surgical techniques will in fact improve rapidly enough to make artificial repair possible
within not many decades, so that genetic approaches will not be required. However, I also
feel that it is unwise to describe as “surely unreasonable” the prospect of restoring to humans
a biological repair capacity that exists in other vertebrates. Vertebrate genomes vary quite
considerably at the sequence level, but hardly at all at the level of the gene; thus it is possible
to study almost any genetic interaction in one vertebrate and apply the resulting knowledge
to another. The cascade of genetic events involved in regenerating a complex structure is
obviously very intricate, but it is no less studyable for that—indeed, it is virtually the same
as studying embryonic development, which is of course a flourishing field of biology. A
recent review 9 noted that, though we certainly do not yet know how to stimulate such
regrowth in mammals, there appear to be no showstopping barriers to the development of
such therapy. There is even a residual ability of some mammals to regenerate somewhat