Aubrey's "survival of the slowest" hypothesis

Aubrey de Grey ag24 at
Wed Apr 11 15:45:46 EST 2001

Iuval Clejan wrote:

> If better ATP producing mitos are degraded faster (because of more
> membrane damage etc), and if the cell regulates mt replication primarily
> based on ATP availability, then in order to keep up ATP production, the
> number of mitochondria in non replicating cells (whose mitos suffer some
> progressive unrepaired DNA damage which degrades their ATP production)
> has to increase.

Yes -- in those that suffer such DNA damage.  Whenever a mutation occurs,
or at least whenever it occurs and that gets the luck of the mitochondrial
replication draw for a while so that it expands to several copies, it gets
clonally expanded to take over the whole cell.  (That's not SOS, it's an
observation that SOS claims to explain.)  But until that time, there are
few or no mutant mtDNA molecules in the cell, so mitochondrial numbers do
not have to rise.

> Has this been observed experimentally?

Yes.  The phenomenon is normally called "ragged red fibres".  It has been
extensively studied in mitochondriopathies (mtDNA-linked diseases), where
a high proportion of certain cell types are mitochondrially mutant; these
cells with a hyperproliferation of mitochondria have indeed been shown to
be the ones with the mutant mtDNA.  Exactly the same is found in normal
aging (though in far fewer cells).

Aubrey de Grey

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