The Mitochondrial Free Radical Theory of Aging
Aubrey de Grey
ag24 at mole.bio.cam.ac.uk
Tue Nov 9 10:13:44 EST 1999
> It seems to me that Wallace's model does account for preferential
> amplification of mutant mtDNA in non-dividing cells; depending on rate
> of cell division versus mitochondrial division within a cell between
> divisions, it might not be ruled out by the fact that the amplification
> is not seen (or is seen to a far lesser degree?) in dividing cells. Is
> there any work that measures these relative rates, or some way to
> actually test what's going on it cells?
Hm, there's a difference between a model accounting for some data and a
model not being ruled out by some data. It may be possible to embellish
Wallace's model with tricks that stop the mechanism working in dividing
cells, but in and of itself it should work at least as well there as in
postmitotic cells. However, as you say, it would be better yet to have
a direct measure: as yet the only one I know of is in yeast, which also
exhibit this phenomenon (it's called "suppressiveness") and which have
been shown not to replicate the mutant mtDNA any more often than the
wild-type (see Chambers and Gingold, Current Genetics 10:565-571).
> Not a happy thought.
No need for such pessimism! It just focuses the design of interventions
> Could we somehow just periodically override the nucleus and get all the
> good mitochondria to replicate a couple of times? In between, it would
> be business as usual in the cell. Or am I just writing science fiction?
Not necessarily -- but I can't think of a way to do that.
Aubrey de Grey
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