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Are AGEs and Lipofuscin related? Could ALT-711 eliminate lipofuscin?

Aubrey de Grey ag24 at mole.bio.cam.ac.uk
Sat Jan 9 08:50:14 EST 1999

Hazel (I presume) wrote:

> Hmmm, couldn't someone just zap the mouse with radiation?  Or would
> that not work because it  would cause mutations in other organelles
> and not just mitochondria?

Spot on (except that mitochondria are the only organelles that have
any DNA -- the nucleus, where all our other DNA, isn't classed as an
organelle).  What one needs is a system that selectively accelerates
the accumulation of mutations in mtDNA and has no other direct effects.
A really promising advance in exactly this area was made recently: it
turns out that mice with only one working copy of their mitochondrial
superoxide dismutase exhibit several typical signs of accelerated free
radical damage inside mitochondria, but no detectable acceleration
outside.  See Williams et al, J. Biol. Chem. 273:28510-28515.  This
includes mtDNA oxidation damage, but (crucially) there is not yet any
data on irreversible damage, ie mutations.  However they are reported
to have a normal lifespan, so we may have some answers soon.

> I guess one would have to speed up the work inside the mitochondria,
> which would make more free radicals.  That is what causes
> mitochondrial DNA damage, right?  So to speed up mitochondria, what
> about exercising one group of mice more than another?

A very FAQ, and rightly so.  I usually ask it as "Why is Carl Lewis
still alive?".  The answer is self-kickingly simple when you hear it,
though: training.  When one does a lot of exercise, one's respiratory
CAPACITY rapidly rises to match; this involves, centrally, a rise in
the number of mitochondria per cell.  So each mitochondrion of a heavily
exercised mouse is doing no more than those of an un-exercised mouse.
(Maybe a little less, in fact.)

Aubrey de Grey

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