Current Research Into Telomeres III

Aubrey de Grey ag24 at mole.bio.cam.ac.uk
Fri Sep 4 08:43:11 EST 1998


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).

Aubrey de Grey



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