The Mitochondrial Free Radical Theory of Aging

Magnus Lynch mdl24 at cam.ac.uk
Mon Nov 8 22:13:27 EST 1999



Aubrey de Grey wrote:
> 
> Magnus Lynch wrote:
> 
> > Aubrey, are mitochondrial proteins expressed on MHC I? If so it would
> > conceivably be possible to immunize against common mutant versions of
> > mitochondrial proteins thus utilizing the immune system to selectively
> > remove these cells. I haven't seen your book so maybe this is one of the
> > possible methods which you discuss.
> 
> Nice idea, but only applicable to mutations which cause the synthesis
> of mutant versions of mitochondrial proteins, and not to mutations which
> cause a failure to synthesise any protein at all.  The latter turn out
> to be more common, because (a) the mitochondrial tRNA genes are hotspots
> for point mutations, and (b) point mutations are anyway probably less
> common than large deletions which completely remove one or more tRNA
> genes.  The tRNA genes in the mtDNA are all essential (no duplicates),
> so such mutations cause non-synthesis of any of the 13 proteins.
> 
> Aubrey de Grey


How about engineering a virus which only replicates in mammalian
mitochondria (as opposed to nucleus/cytoplasm) and which can only
replicate when the free radical concentration in a given mitochondria is
substantially less than normal. This virus would, thus only reproduce in
the mitochondria implicated in your "reductive hotspot hypothesis". If a
distinctive peptide was coded for in the viral genome it could be
inferred that cells expressing this peptide on MHC I have defective
mitochondria. Immunisation against this peptide would selectively kill
the cells responsible for the "reductive hotspot hypothesis".

Magnus Lynch





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