The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki

CHAPTER 14
Ablation of Anaerobic Cells:
Techniques and Hurdles
14.1. Apoptosis: A Ready-Made Cell Killer
The death of cells is not always something that the body seeks to avoid. There are two
major pathways involved in cell death, called necrosis and apoptosis; apoptosis is the one
that will be highlighted here, because it has features which appear quite readily
amenable to recruitment for the purpose under discussion. One is that it is a highly orderly,
regulated process, so that once initiated by means that we engineer it is likely to proceed
“hygienically”—that is, without toxic consequences for healthy cells nearby. (Necrosis should
not be discounted, however—see Section 14.5.)
The other feature of apoptosis which may be of particular use is that it occurs during
embryonic development: it is used in the construction of large-scale features such as the
capillaries of the kidney. This means that the body is somehow able to generate a signal that
induces certain cells to enter the apoptotic program while other cells very nearby do not.
The cells cannot be acting purely independently of each other, since in that case the structure
that resulted would not have the necessary organisation. And that is why the signal we
engineer, which causes anaerobic cells to enter apoptosis, need not necessarily be a genetic
signal, delivered by as yet unperfected gene therapy. In fact it may not need to enter the cell
at all, since (as noted in Section 9.4) these cells should have easily detectable surface features
such as a highly up-regulated PMOR.
14.2. Specificity and Frequency of Treatment
Any medical treatment that is designed to induce changes—in this case, death—in
some cells but not others has an inherent risk of inaccurate targeting: both of inducing the
changes in cells where they are not wanted, and of overlooking cells where the changes are
wanted. Since this treatment has not even begun to be developed, we of course can have no
idea how prone it will turn out to be to either class of error. All we can say is what scale of
error rate is likely to be acceptable for the purpose.
In particular, there is a trade-off between how accurate the treatment is in targeting the
correct cells and how often it will need to be administered. If the ablation of anaerobic cells
could be done perfectly, MiFRA predicts that the rate at which cells will enter SOS thereafter
would revert to that of a young individual, and would not return to the level it had before
that first treatment until the individual was perhaps one and a half times as old as they were
then. (Not twice as old, because MiFRA only asserts that mtDNA decline is the dominant
determinant of lifespan, not that it is the sole one.) By this reckoning, treatment would only
need to occur every few decades. In practice, it is unrealistic to expect every single anaerobic
cell to be removed each time, so treatment would have to be more frequent than that.
The Mitochondrial Free Radical Theory of Aging, by Aubrey D.N.J. de Grey.
©1999 R.G. Landes Company.