BIOMED: postponing aging [was MISREGULATION OF MITOSIS ...]

From: Robert Bradbury (bradbury@genebee.msu.su)
Date: Sun Jun 11 2000 - 23:17:54 MDT


On Sun, 11 Jun 2000 GBurch1@aol.com wrote:

> In a message dated 6/7/00 2:53:03 AM Central Daylight Time,
> eugene.leitl@lrz.uni-muenchen.de writes:
>
> > [snip]
> > 2) The authors report their results suggest that an altered
> > expression profile of genes involved in mitosis occurs with age,
> > and that 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]
>

Note that they are talking only about *mitosis*, which is only
going to apply to epithelial tissue (skin, stomach/gut, lungs),
blood components (esp. immune system) and other tissues derived
from slowly dividing (liver in some cases) or stem cell lines
(perhaps a very low level in the brain).

Many of your major terminally differentiated organs: heart,
pancreas, kidney, most of the brain *are not* covered by their
conclusions.

I would put the conclusions in the Dysdifferentiation and/or Error
Catastrophe theories of aging.

> This seems to be a very fruitful line of research that may lead to a good
> insight consistent with the common sense experience of aging as a
> deterioration of many bodily functions and structures on a broad front at
> different rates.

Yep, I've been of the opinion for more than 5 years if you know what
is going on in the cell at the gene expression level, you will be
able to understand the treatments necessary to push the cell back
to a "youthful" pattern (if the program is mostly intact!).

> Assuming this is borne out, what kinds of strategies to
> combat this phenomena occurr to our resident biomed experts?

It really depends on the cause. It isn't clear how they conclude
somatic mutation rates are increased, but if so (and I've always
been partial to this theory), it means the only *real* solution
is to replace the genome. That requires hard nanotech and is
discussed in Nanomedicine. It isn't spelled out, but the
implication I see from Sections 10.4.2 (Mechanical Cytocide
and Virucide), 9.3.5 (Materials Disassembly for Disposal)
and 9.5.4 (Nucleography) is that you can remove the old
grungy (highly specific medical terminology here) DNA and
synthesize new DNA from tapes kept onboard the nanobots.
I've had private conversations with Robert Freitas about
this and I think it will be discussed in further detail in
subsequent Nanomedicine volumes and/or future papers.

Prior to the hard nanotech era (with good engineering capabilities),
you should be able to get some spin control on the failures
that are occuring with supplemental nuclei in the form of
bacteria engineered to produce non-mutated RNA's at the right
point in the cell cycle. The problem will be the limited
carrying capacity of bacterial genomes for augmenting human
genome program failures. Applying "gene therapy" patches
with specific virus-derived machinery might be possible,
but given the large number of possible mutations, the
simple volume of engineering required is probably
prohibitive (you need tens of thousands of "correctors"
to replace various damaged genes).

Finally, you have whole organ replacement. This is for example
feasible with bone marrow transplants (for immune system
reconstitution) or skin today (with some minor details still to be
resolved like hair follicles). Of course this involves fairly
invasive and expensive procedures currently.

It is worth noting that people who are *serious* about anti-aging
should go to the trouble of either getting some blood and/or
bone marrow frozen (the bone marrow contains lots of hematopoetic
stem cells, the blood has low but detectable concentrations)
so they could use it in the future to treat the age-related decline
of the immune system. Skin plugs would get some fibroblasts
and muscle biopsies might get some myoblasts, that are useful
for regrowing other tissues.

I know that there are companies that provide such services.
Our medical experts and/or super-sleuths might want to investigate
and organize a page of sources for such treatments that we can add
to the ExI website. IMO, such pre-aged preparations are at least
as important as popping a bunch of antioxidants every morning, though
they are more time consuming and expensive.

Robert



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