Mitochondria oxidative damage?

David Cassarino dsc9w at avery.med.Virginia.EDU
Fri Aug 2 12:20:21 EST 1996


mfossel at aol.com  writes:
> Hello Gary.
> 
> Mitochondria are one of the driving sources of aging damage within cells: 
> they produce about 95% of the free radicals and as the cell "ages", they
> leak.  You are, of course, right about the maternal source of mitchondria.
>  Remember, however that the maternal *germ cell* line of mitochondria has
> not shown and sign of aging in the past 1-2 billion years since this
> particular organelle first took up permanent residence within eukaryotic
> cells.  Although (retrospectively in surviving germ cell line
> mitochondria) they have not age, they show oxidative degradation within a
> few decades in human somatic cells.  This implies that non-mitochondrial
> (eg, nuclear genes, etc) factors determine mitochondrial "aging", not
> merely mitochondrial damage *per se*.  

Not necessarily.  Mitochondria in the maternal germ cells are
basically inactive (there may not even be any oxidative
metabolism in dormant germ cells-?) compared to mitochondria in active neurons
and other cells.  I don't know the actualy numbers, but the
amount of free radicals produced by respiring mitochondria is
probably many orders of magnitude greater than that produced by 
dormant germ cell mitos.  So it is no wonder that most damage
to mito DNA occurs in somatic cells, and may not even be
detectable into adulthood.  CNS neuronal mito DNA is also
especially vulnerable to damage due to relatively large free
radical production (especially in catecholaminergic cells, like
the substantia nigra, which decays in Parkinson's disease) and
insufficient free rad defenses. 

Also, natural selection would tend to eliminate those mitos in
the germ line that had significant mutations--or at least those
embrios unlucky enough to inherit them!

Telomere theory of aging suggests
> that homeostatic defences against (among other things) mitochondrial
> oxidative damage are "down-regulated" as the telomere shortens.  Far from
> being mutually exclusive, mitochondrial damage plays a pivotal role in the
> intracellular aging process in telomere aging theory.  The same in true of
> cumulative DNA damage (and down-regulation of DNA repair), protein
> turnover rates, etc.  Thanks for your thoughts:  you are pretty close to
> hitting the nail on the head
> 
> Best wishes,
> Michael Fossel, MD, PhD
> Author, Reversing Human Aging
-- 
David S. Cassarino              "The mind is not a vessel to be filled
MSTP, Neuroscience 2nd Year          but a fire to be kindled."               
UVA School of Medicine                   -Plutarch
dsc9w at virginia.edu          




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