Telomeric Theory - Related Reseach - Mitochondria
excelife at earthlink.net
Wed Sep 30 04:52:23 EST 1998
V. RELATED RESEARCH
B. Free Radical & Mitochondrial Theory
The telomeric theory of aging seems to explain the causes of replicative
decline and senescence associated with aging in replicating cellular systems.
But some human cells, most notably muscle and nerve cells are post mitotic
and do not normally reproduce.
The causes and alleviation of aging in these non-reproducing cells will be
required for any strategy to extend the human life span.
The free radical theory of aging has proposed that the accumulation of damage
caused by free radicals, (ie; molecules with unpaired electron), may
contribute to cellular decline and aging. Since cellular reproduction
eliminates or repairs much of this damage, it was suggested that the effects
of the free radicals would be more noticeable and cumulative in
Further, the theory indicates the damage would be the greatest in the
mitochondria since they have been shown to be a major source of free radical
oxygen molecules. This damage could interfere with cellular respiration
leading to the declines seen during aging.
The research has supported much of this theory by showing "A causal
relationship between oxidative modification and mutation of mtDNA." Also
that "mitochondrial RNA (mtRNA) declines are associated with life
expectancy." And "an age-related decline in mitochondrial respiratory chain
Unfortunately, most experiments to modify these processes have failed to
achieve significant results, with a few notable exceptions. The research
into the fly Drosophila melanogaster did show some longevity benefits with
the reduction of free radical damage. Since the cells of Drosophila
melanogaster are post mitotic this may provide some clues on how human muscle
and nerve cells age.
An interesting proposal to mitigate the damage to mtDNA has been proposed by
Aubrey de Grey at Cambridge Univ. He has suggested experiments wherein "we
could use "nuclear mtDNA" to construct the 13 proteins, (coded for by mtDNA)
outside the mitochondria, and then import those proteins into mitochondria
where they can do the job that the ones encoded in the damaged mtDNA are
failing to do."
There are several technical obstacles to achieving this but if they can be
worked out, much of the age related declines noted in the mitochondria above
may be alleviated and the effects on non-replicating cells could be extended
or even permanent viability.
It has been suggested that this alone may have a significant impact on life
span. But if not, then its actions in non-replicating cells combined with
telomeric lengthening to maintain the viability of the replicating cells
could move us closer to achieving our goal.
(Next: Genetic Effects on Aging)
Thomas Mahoney, Pres.
Lifeline Laboratories, Inc.
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