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

From: Rafal Smigrodzki (rafal@smigrodzki.org)
Date: Sat Apr 05 2003 - 23:14:45 MST

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    ----- Original Message -----
    From: "Robert J. Bradbury" <bradbury@aeiveos.com>
    To: <extropians@extropy.org>
    Sent: Friday, April 04, 2003 5:47 PM
    Subject: Aging: don't go there [was: manganese SOD and CR]

    >
    > 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.
    >
    ### I keep debating the related problem of mitochondrial mutations in PD
    about once a day with my boss and other people, and I can only concur - we
    know little, the system is complex, methods crude. But, we are moving
    forward, step by infinitesimal step. I started recently working with a laser
    capture microscope and we have some ideas about how to nail the mutations,
    which we know simply *must* be there, but haven't been found, despite dozens
    of people working on it.

    Give us a couple million $ and an extra sequencer or two, and we'll get
    them. Guaranteed.

    No beach lounging for me :-)

    Rafal

    BTW, I agree with Mez's skepticism about the article I quoted.



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