Aging: don't go there [was: manganese SOD and CR]

From: Robert J. Bradbury (bradbury@aeiveos.com)
Date: Fri Apr 04 2003 - 15:47:39 MST

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    On Fri, 4 Apr 2003, Ramez Naam wrote (among some other things):

    > My first reaction is a bit skeptical. Creatures with increased SOD
    > production don't act like CR creatures. CR creatures are smaller and
    > have lower fertility.

    [many snips]

    I would strongly suggest *not* going there (in attempting to make sense
    of this at this time).

    Yes the mitochondria produce free radicals -- this appears to be related
    to the "throughput" of the mitochondrial respiratory chain [when it gets
    backed up more free radicals get generated] -- but one of the life-extending
    mutations in C. elegans involves insufficient Co-Q9 or Co-Q10 (so the
    mitochondrial transport chains get backed up, do suffer reduced transport
    capacity and perhaps greater free radical generation. But this may be
    offset by the reduced ATP generation (effectively CR). But then in mammals
    you have the uncoupling proteins (which serve to facilitate heat production and
    would reduce the backup in the mitochondrial transport chains) (I posted
    extensively about this probably about a year ago). But they might generate more free
    radicals if the free radical production is an inherent part of the respiratory
    glucose/oxygen consumption process. (I.e. more heat == more free radicals).
    But then the free radicals could be offset by anti-oxidants such as
    estrogen or alpha-lipoic acid that may not be present in large quantities
    in more primitive organisms.

    If one wades into this one is wading into one of the most complex
    intellectual problems I'm aware of -- and given the state of our
    knowledge base I personally don't think resolving it isn't going
    to be pretty.

    Go relax on the beach -- let the grad students that actually
    need to debate these things deal with it.

    R.



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