[extropy-chat] AGING: New Theory

[Aubrey de Grey]

> Well (Van Remmen, 2003 [1]) is interesting in that free radicals seem
> to be contributing to cancer but not to ageing.

Nearly but not quite -- what it shows is that free radicals accessible
to antioxidant enzymes do not contribute to aging.  (and, as you say,
this is only in lab mice, not humans and not even wild mice.)  This is
important because there is a distinct possibility that superoxide does
most of its harm before it reaches a location where SOD can get at it.
I suggested in 2000 (JAAM 3:25) that the action might be occurring in
the intermembrane space, where superoxide might be protonated rather
more often than elsewhere (more acidic because of proton-pumping by
oxidative phosphorylation).  The protonated form of superoxide is a
really nasty species (see my subsequent paper DNA Cell Biol 21:251),
in contrast to the tameness of superoxide itself.  There are actually
a few weakneses in my proposal, but they were neatly eliminated by an
idea proposed by Florian Muller a few months later (J Am Aging Assoc
23:227): he looked hard at the structure of Complex III and realised
that protonated superoxide could be formed within the actual membrane
itself (in the lipid phase), and zap a fatty acid or protein at once.
Coincidentally Muller is now a coworker of Van Remmen in San Antonio.

Cheers, Aubrey