Obstacles to The Telomeric Theory of Aging
excelife at earthlink.net
Wed Sep 16 04:24:32 EST 1998
IV. CRITICISMS, NEGATIVE FINDINGS & OBSTACLES
Besides the theoretical problems of non-replicating cellular systems and
telomeres relationship to age-related genetic expression, there are a number
of more mundane obstacles to the research.
The first is in identifying what we're talking about. Determining the length
of telomeres at the ends of the chromosomes and finding where telomerase is
active are no easy matters. Fortunately recent research has provided tests
such as fluorescence in situ hybridisation (FISH) for analyzing telomeres
and a non-isotopic telomeric repeat amplification protocol (TRAP) for
determining telomerase activity in bones have been developed. Additionally
Lawrence Berkeley Labs Life Sciences Div. has produced a "kit" for
identifying senescent cells in-vivo. More powerful methods may be required
for future research but here the research is on the right track.
More troublesome are the procedural methods and protocols that may be
required to implement therapies based on the telomeric theory of aging.
Assuming, for arguments sake, that the introduction of hTR or hTRT into a
cell could restore its youthful viability, what vectors are available to
deliver it to the desired cells?
Some recent research into mammalian artificial chromosomes has shown how
alpha-satellite DNA can seed centromeres in human cells suggesting that they
have the potential to be developed as gene delivery vectors. This gets us
across the cell wall and into the cell itself but whether it can be
generalized to do this, in the manner and quantity required, remains to be
seen. This and other research into vectors suggest that delivery may not be
a major problem.
Once in the cells in vivo, however we may run into some other problems. None
of these problems have yet been encountered but given Murphy's Law...
Some of these problems could be that the cellular maintenance system,
possibly including genetic control of telomeric length, (similar to that
shown in mice), could interfere with the process. The lengthening of the
telomeres might be seen by the cells maintenance system as a defect and the
cell might initiate apoptosis. The change in telomeric length might have a
negative impact on age related genetic expression causing either
in-appropriate proteins to be produced or necessary proteins not to be
produced. These are just a few potential problems but they help point out
some of the complexities that may be encountered.
Additionally, it appears that replacing telomeric length in and of itself
does not cause a cell to replicate. This may be beneficial for worries about
cancer but if the purpose of the "therapy" is to replace lost cellular mass
then some additional step may be required. And once the cell does divide it
still needs to be integrated into it's proper environment.
Many of these problems are related to and controlled by "normal" genetic
expression. If telomeric length is shown to be a factor in determining this
genetic expression, as is suggested by their role in transcriptional
silencing in the yeast, Saccharomyces cerevisiae, then some of these problems
may solve themselves.
There will, almost undoubtedly, be some problems and obstacles in our search
for longevity through the research into the telomeric theory of aging but
none that appear insurmountable and given the goal, well worth the effort to
(Next: Related Research)
Thomas Mahoney, Pres.
Lifeline Laboratories, Inc.
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