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SOD and Downe's Syndrome

Aubrey de Grey ag24 at mole.bio.cam.ac.uk
Thu Sep 3 09:02:09 EST 1998

Cathy Woodgold wrote:

> Might it be feasible to treat Downe's Syndrome by putting more of the
> latter type of enzyme into the person, perhaps by daily injections?
> (Or by consuming the nutrients needed for that enzyme (selenium??))
> If we can find effective treatments for Downe's Syndrome, it
> might help us find anti-ageing treatments for everyone.

to which I replied:

> Some studies have been done on this -- a search in Medline using the
> string "down's syndrome catalase" works quite well.  I don't know any
> more, but I also found a reference (Int J Dev Biol 1989;33(1):183-188)
> which notes that glutathione peroxidase (the other hydrogen peroxide
> destroying enzyme) is not upregulated in response.  The abstract doesn't
> give any theory why not, though.
> I will look up the above paper and others and maybe
> post something more illuminating in due course.

In exploring this topic further I have come across the recent work of
Ismail Kola at Monash, Australia, which is very informative and exciting.
I particularly recommend Cristiano et al., Mech Ageing Dev 80:93-105 and
de Haan et al., Human Mol genet 5:283-292.  The upshot of this work is
twofold.  One conclusion is that hydrogen peroxide is bad for cells,
causing senescence-like phenotypes.  The other is that the brain and the
small intestine, but none of many other tissues examined, show a rise in
SOD activity with age that is not paralleled by either catalase or
glutathione peroxidase, and that they are also the tissues which show a
significant rise in lipid peroxidation (though their actual data do not
look very good to me on this last point).  This was done in mice.  Again
there is no speculation as to why the brain and small intestine do not
up-regulate catalase or glutathione peroxidase.  The interpretation of
this work is hampered by the fact that there are five distinct types of
glutathione peroxidase, two of which are present in most tissues.  It's
clearly a fruitful line of investigation, though.

Aubrey de Grey

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