Current Research Into Telomeres III
tmatth at netcom.ca
Fri Sep 4 21:15:23 EST 1998
Aubrey de Grey wrote:
> Tom Matthews wrote:
> > When I wrote the above statement, I knew that I might be slightly
> > overstating the case re mtDNA mutations. But is it not true, at least,
> > that mitochondrial "decline" (whether caused by mutations or not) is a
> > clear cause of some aging pathologies? The examples, of dementia and
> > weakened hearts come to mind.
> That is quite true (or, at least, very well supported by the evidence),
> but the distinction between (a) mitochondrial decline due to mtDNA damage,
> and (b) mitochondrial decline without mtDNA damage, is absolutely pivotal
> -- it cannot be overstated. Since mitochondria continue to divide in
> all cells, and since everything in a mitochondrion other than the mtDNA
> is constructed from scratch when it divides, damage to "mt-non-DNA" CANNOT
> accumulate autonomously. Every time a mitochondrion divides, that damage
> is diluted away; it can only be reintroduced (and then increased) from an
> external source.
> In other words, mitochondrial decline without mtDNA damage is in the same
> boat as AGE accumulation, free radical damage to cellular components other
> than mitochondria, etc: it may be caused by mtDNA damage in mitochondria
> of other cells (as I've proposed), or by telomere shortening (as others
> have proposed), or by something else, but this "ultimate" cause has got to
> be a change in something which isn't recycled (or which is recycled only
> by copying, like DNA).
So what this amounts to, in general, appears to be that we can (and
should) divide all of the various theories of aging into those which are
secondary or "derivative" and those which are primary or "ultimate".
Among those which are derivative would be free radical damage and AGE
accumulation. Among those which are ultimate are mtDNA damage/change (in
non-dividing cells only and DNA damage/change (whether due to telomere
shortening or otherwise) in both dividing and non-dividing cells (can
there be anything else which is "ultimate"?). Furthermore, it appears
that research is at the stage where there is good evidence that certain
derivative aging changes are implicated in specific aging pathologies,
but the evidence for implication of any ulimate aging changes is weaker
(although there clearly *must* be "ultimate" causes).
Aubrey, if you agree with my classification description above, would you
be so kind as to list which of the various aging theories are in which
categories and furthermore which primary theory (or theories) the
various secondary theories are derivative of.
OTOH, if my classification idea is not good, would you please describe
why not and tell us if there is any such classification (and then again
which theories are in which categories and why).
If this is too much work, too large to be presented here, or is
available elsewhere, just let us know.
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