DNA damage paradoxes

Timothy R. Hughes th035681 at mbcr.bcm.tmc.edu
Tue Mar 22 14:24:17 EST 1994

I am about curious about a couple of things:

1)  If any kind of universal, irreversible cellular damage (to proteins,
    DNA, lipids, cell structure, whatever) is responsible for
    aging, then how is it that the germ line cells manage
    to escape this and go on to make a new organism with 
    a reset "biological clock"?  Deleterious mutations
    do not seem to arise with overwhelming frequency, as evidenced by
    the ability of some women to have ten or twelve healthy
    children.  The germ cells must undergo oxidative phosphorylation,
    or they will die from inability to maintain membrane 
    gradients if nothing else.  If there's a selection scheme for
    the best eggs and sperm, how would it work for genes which aren't
    expressed - for example, liver, muscle, and CNS-specific genes, which
    between the three represent probably more than half the genome?
    Is there something magical about meiosis or fertilization?

2)  Why is it that some of the so-called "accelerated aging" syndromes
    are thought to be mismatch repair deficiencies, and yet individuals
    with HNPCC, who also clearly have at least one mismatch repair defect,
    do not suffer accelerated aging?  
-- Tim Hughes

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