AGING: Accumulation of DNA damage

From: Robert J. Bradbury (
Date: Mon Jun 26 2000 - 11:18:42 MDT

As I've stated for may years (since my comments in the early
'90's on and bionet.molbio.ageing),
DNA damage accumulation *should* be part of aging.
I base this entirely on the observation that mutations
are known to accumulate and in single cells that get
amplified lead to cancer. We have little idea what the
mutations may be in non oncogene/tumor-suppressor genes
with the exception of some work done in the HPRT
gene (R. Albertini comes to mind) and some work
that I believe has been done in blood group genes
though the details slip my mind at the moment.

At any rate, many may be interested in "The Second Creation:
Dolly and the Age of Biological Control", by Ian Wilmut,
Keith Campbell, Colin Tudge (Farrar, Straus & Giroux).
Reviewed in July 2000 Discover, pg 116. The quote which
caught my eye:

"For ethical and other reasons, the authors do not condone
the most unsettling use of cloning to create human genetic
duplicates. In the authors' experience, clones are 10 times
more likely to die in the womb and three times more likely to
die after birth. They are also more likely to have deformities."

Now, so long as the cloning is done in a way to remove the brains,
I think the ethical issues are specious, but this *does* raise the
point that you may have to do 30 clones to get one good one
(if you are interested in whole body transplants).

It does however in my mind provide a significant amount of gravity
for the DNA Damage theory as being a factor in the aging process.
The developmental genes in an adult can accumulate mutations and
you will never know it. But if you try to grow a new adult using
those genes with accumulated mutations, then the results detailed
above are a likely result. It also suggests that if DNA mutations
are gradually causing deaths in the latent stem cell population
in the body, that over time you will have less and less reserve
capacity from which to renew yourself. Only if you can reactivate
the program that *expands* the remaining subset of "perfect" stem cells
(as probably happens during development) will you be able to
revserse this aspect of the aging process.


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