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Telomeric Theory - Related Reseach - Mitochondria

Excelife excelife at earthlink.net
Wed Sep 30 04:52:23 EST 1998


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 
non-reproducing cells.

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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