From: Robert J. Bradbury (bradbury@aeiveos.com)
Date: Mon Apr 07 2003 - 08:44:47 MDT
On Sun, 6 Apr 2003, Rafal Smigrodzki wrote:
> ### I keep debating the related problem of mitochondrial mutations in PD
> about once a day with my boss and other people, and I can only concur - we
> know little, the system is complex, methods crude.
Rafal, could you explain "PD"?
> I started recently working with a laser capture microscope and we have
> some ideas about how to nail the mutations, which we know simply *must*
> be there, but haven't been found, despite dozens of people working on it.
I wouldn't say they haven't been found -- but would agree that they
haven't been found in the quantities one would expect for increased
free radical production to be considered a major cause of aging.
*BUT* if one has a cascade effect -- increased mitochondrial FR
production leading to increased double strand breaks (in the nucleus)
that trigger apoptosis -- *then* you have a real scientific problem --
"*How* do you find something that "disappears" almost as fast as it is
produced?" [In this case aging is a very gradual process because you
are losing cells that are only being replaced to a limited extent
by circulating stem cells -- which may themselves be a declining
population.]
> Give us a couple million $ and an extra sequencer or two, and we'll get
> them. Guaranteed.
I don't think so if the above scenario I've outlined is the case.
Rafal -- seriously -- do some thinking about cascade effects.
I've got a fairly robust theory of aging that I call the "energy
catastrophe theory of aging" involving the improper repair of
double strand breaks causing increased production of proteins
that will not fold properly whose production and breakdown
produces increased demands on energy production, free radicals
from which in turn produce even more double strand breaks.
If this is correct then one has the problem of looking for
something that simply isn't going to be there!
It requires some much more complex methods such as measuring
the percentage of proteins that are produced and will not
fold correctly and must therefore be broken down -- plus
some assessment of the rates of apoptosis -- plus some
analysis of the rates of the production of new mitochondria
(due to increased energy demands).
As I said -- it is *not* an easy problem.
(If you email me offlist, I've got a very rough draft of notes
and references on this that you may want to review.)
Robert
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