X-Message-Number: 26230
From: "mike99" <>
Subject: Fwd: Mice offspring of older moms die younger
Date: Mon, 23 May 2005 16:16:30 -0600

From: "Robert J. Bradbury" <>
Date: Fri, 20 May 2005 17:39:33 -0700 (PDT)
To: Gerontology Research Group <>
Subject: [GRG] Longevity decrease in children of elderly parents.
Reply-To: Gerontology Research Group <>


I'm sure Leonid will be interested in this.  Stan and others
involved in the supercentenarian research might be as well.

Scienceblog is reporting:
 "Mice offspring of older moms die younger".
 http://www.scienceblog.com/cms/node/7954

This is consistent with my "Grand Unified Theory of Aging"
that no matter how you slice it genome mutations due to
double strand break repair (actually mis-repair) gradually
corrupt the genomes of individual cells.  The longer a cell
has been around the more likely it is to contain errors.
(Major errors show up as decreased fertility or miscarriages;
minor errors show up in the decreased longevity of ones offspring.)

On this point Aubrey and I are in rather sharp disagreement.
Speaking to his specific point of "Chromosomal mutations and
how to obviate them" [1].  I believe that he underplays the
significance.  If the genomic mutations are accumulating in
the germ cells then this obviously has a health-span impact
upon ones children (as cited above).  What is less clear is
precisely what the negative impact of individual nuclear (genomic)
DNA mutations is within each cell which do not happen to mutate
with tumor suppressor genes or oncogenes (which are perhaps
only 2-5% of the potential targets in the genome -- depending
upon how many genes are active in a particular cell type)?
I.e. if you are *not* mutating tumor suppressor genes or oncogenes
you *are* mutating other genes -- *some* of which are essential
for the robust performance of the cell within whatever niche
it occupies within the body.

E.g. Neurons do not normally replicate and so cancer is hard to
induce in neurons.  But day-in and day-out they may be subjected
to genome altering nuclear DNA mutations.  The same is true for
both eggs (where there is some open question with regard to
whether or not precursors are available and the extent to which
they replicate) and sperm (where the precursors obviously
replicate but we may not have a clear picture with respect
to what kind of selection is taking place to eliminate those
with significantly defective genomes).

My suggestion would be to come around full circle... If viable
organisms are dependent upon trillions of cells with "functional"
genomes and reproduction is dependent upon two "functional"
genomes that happen to connect we really need a better picture
of how much (and at what rates) damage accumulates that make either
survival or reproduction extremely doubtful activities.

Robert

1. http://www.gen.cam.ac.uk/sens/cancer.htm

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