The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki

Prospects for Intervention
will be before this research succeeds in perfecting a safe, reliable treatment. All that can be
said is that there are many labs around the world trying to achieve it, that they are employing
a wide variety of techniques, and that they are constantly reporting encouraging progress in
trials. This has led, importantly, to increasing public optimism about timescales on the part
of specialists. 9 If forced to guess, I would say that truly general-purpose techniques for DNA
delivery to somatic cells will probably achieve a level of reliability sufficient to gain
governmental authorisation within 20 years, though almost certainly not within 10 years.
Consequently, I believe that safe gene therapy may have become widely available by the time
all the other problems with these proposed interventions are solved.
13.4.2. What Could It Achieve in Regard to Aging?
Again, no one really knows. By the time it is available, however, we may have a more
accurate idea. This is because there is a far simpler technology, already routine in many
laboratories worldwide, with which we can simulate the effects of perfect gene therapy in
mice. Mice are not men, so the effect achieved in mice might not be an absolutely reliable
indicator of what could be done for humans, but it would certainly be a broad hint.
This simpler technology is called germ-line transformation. Functionally, it is the same
as gene therapy except for the target cells. Gene therapy targets somatic cells, which make up
almost all of our body but are not passed on to our offspring. Germ-line transformation
targets egg cells, which (when fertilised) give rise to all the cells that form the embryo. This
means that germ-line transformation is far more dangerous for humans, and also is of no
benefit to those of us who are already alive. But it can be used in mice, and since mice have
such a short lifespan it can give us hugely valuable information quite quickly.
Therefore, the likely scenario for option h (obviation of mtDNA) is that we will be able
to “prototype” the whole treatment, and therefore test the whole theory laid out in this
book, by generating mice with appropriately modified genes of the mtDNA in the nuclei of
all their cells and, well, just sitting back and watching them age—or not, as the case may be.
If their lifespan is indeed increased significantly, efforts to apply the same treatment to humans
using gene therapy will become motivated.
References
1. Holmes DJ, Austad SN. Birds as animal models for the comparative biology of aging: A
prospectus. J Gerontol 1995; 50A:B59-B66.
2. Seibel P, Trappe J, Villani G et al. Transfection of mitochondria: Strategy towards a gene
therapy of mitochondrial DNA diseases. Nucleic Acids Res 1995; 23:10-17.
3. Papa S, Scacco S, Schliebs M et al. Mitochondrial diseases and aging. Mol Aspects Med
1996; 17:529-533.
4. Kagawa Y, Hayashi JI. Gene therapy of mitochondrial diseases using human cytoplasts.
Gene Therapy 1997; 4:6-10.
5. Chrzanowska-Lightowlers ZM, Lightowlers RN, Turnbull DM. Gene therapy for
mitochondrial DNA defects: Is it possible? Gene Therapy 1995; 2:311-316.
6. Taylor RW, Chinnery PF, Turnbull DM et al. Selective inhibition of mutant human
mitochondrial DNA replication in vitro by peptide nucleic acids. Nature Genet 1997;
15:212-215.
7. Taylor RW, Chinnery PF, Clark KM et al. Treatment of mitochondrial disease. J Bioenerg
Biomembr 1997; 29:195-205.
8. Balzan R, Agius DR, Bannister WH. Cloned prokaryotic iron superoxide dismutase protects
yeast cells against oxidative stress depending on mitochondrial location. Biochem
Biophys Res Commun 1999; 256:63-67.
9. Verma IM, Somia N. Gene therapy—promises, problems and prospects. Nature 1997;
389:239-242.
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