Re: Summary: "Mitotic Misregulation and Human Ageing"

From: Robert Bradbury (
Date: Thu Apr 13 2000 - 06:55:53 MDT

On Wed, 12 Apr 2000, Al Villalobos wrote:

> Concluding paragraphs from "Mitotic Misregulation and Human Ageing" Science,
> 31 MAR 2000
> "We suggest that an altered expression of genes involved in cell
> division occurs with age. These changes result in increased rates of somatic
> mutation, leading to numerical and structural chromosome aberrations and
> mutations that manifest themselves as an aging phenotype. [snip]

In reading this I was struck by the degree to which they had gathered
together a laundry list of aging phenomena and attributed them to
mitotic disregulation. [Perhaps my bogosity filter running a bit
high...] But it is worth asking why they are quoting presenilin
and Alzheimer's when neurons in the brain *don't (usually) divide.
This is the same (possible) mistake that Fossil makes in his book
when he tries to attribute everything to telomere loss.

> Next step: explaining WHY they change. Comments?

Mitotic Misregulation can easily be attributed to "dysdifferentiation"
(an old theory by R. Cutler), that has as an underlying cause DNA
damage. I said 8 or more years ago in the
discussions that a major underlying factor in aging is the accumulation
of DNA damage. If you randomly change the code of the program sooner
or later the program isn't going to work correctly. This is going
to apply to different degrees to dividing and non-dividing cells
because of the different rates of repair that you get when you have
to copy DNA. It fits nicely with the Werner's Syndrome situation where
a (presumed?) deficiency in DNA repair results in accelerated aging.

This means that effective solutions are going to require (a) replacing
"collectives" of DNA (using whole organs with new DNA); (b) secondary
"nuclei" [from biobots] that add "patches" to the genome as interim
solutions, and finally (c) nuclear abortion and replacement with a new
genome (done in vivo using nanobots). Stem cell "recharging" (neuronal,
immune system, etc.) would seem to offer potential benefits.


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