From: Robert J. Bradbury (bradbury@aeiveos.com)
Date: Mon Oct 15 2001 - 07:30:18 MDT
should get you a long list of articles related to mitochondrial aging.
The first is Aubrey's original proposal about the mechanisms
behind the mitochondrial theory.
You can also search on his name by entering: "de Grey AD"[au] into
the query box (I can't seem to figure out how to make a URL for that).
In summary, Aubrey thinks that mitochondria that experience
mutations or deletions in the mitochondrial DNA are going to
be less efficient at producing free radicals and damaging
themselves. Because they have less damage, they are degraded
less frequently by the lysosomes. Eventually they would
come to dominate the mitochondrial population in the cells. Another
possibility is that if they have deletions in their mitochondrial DNA
they could replicate more quickly allowing them to gradually become
the dominant population.
Cells with diminished ATP capacity (due to the defective ATP
production) may be less able to conduct maintenance and repair
functions and gradually accumulate damage in a increasing spiral
that could lead to cell death. Scientists have demonstrated that
there are cells, esp. muscle cells that do have individual
muscle fibers that have accumulated a population of mitochondria
that have deletions in their DNA. The hard part is tying this
into aging -- if the cells eventually die and effectively
"disappear" and if this occurs at a very slow rate, then
detecting them in the process of doing this is likely to
be difficult.
Mitochondrial aging may only be a problem in tissues composed
primarily of non-dividing cells such as muscles, heart, neurons,
kidneys, etc. and is likely to be a completely distinct problem
from those involving the anti-cancer program, telomeres and the
Hayflick limit which primarily involve tissues with dividing cell
populations.
One can explain the rare presence of mitochondrial defects in
newborns the same way one explains the lack of mutations in general --
organisms have relatively robust mechanisms for detecting
improperly developing offspring and terminating the development.
Its a big waste of resources to be producing offspring with
a reduced ability to survive -- one would expect there to
be a lot of selection pressure against such situations.
Robert
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