Cellular aging [was Re: >H A simulated cell]

From: Robert Bradbury (bradbury@genebee.msu.su)
Date: Wed Jan 26 2000 - 07:09:14 MST

On Tue, 25 Jan 2000, Technotranscendence wrote:

> Also, cryobiology is not the only field I mentioned. Antiaging research is
> the other. What of that? If one can develop a good model of aging at the
> cellular or molecular level, then finding new ways to combat it would seem
> to me to be a lot easier.

Aeiveos Sciences Group started on that with the differential gene
expression studies (at the tissue level). The problem is the technology
isn't available yet to provide the information base at the cellular
level. You could just about do it if you could tease out single
cells from frozen tissues, do quantitative PCR on the mRNA in the
cells and then do differential display analysis (to see how gene
expression levels differ in young, middle-aged and old animals).
But you are talking difficult methods and very high costs here.

You really need the gene expression chips for the human genome *and*
a lab that can use lasers to excise single cells. Otherwise the picture
you get is that of tissue aggregates that tell you little about
"cellular aging". Then there is a separate problem of how you get people
to sit still for a few hundred needle biopsies into various organs (doctors
and hospital facilities to do these don't come cheap). You could do the
studies in mice, but it remains an open question how well understanding
aging in short-lived animals will translate to understanding aging in
long-lived animals. My feeling is that you will get a partial picture.
I'd guess in 3-5 years researchers should be able to begin working
on this aggressively with it only costing half an arm.

> From the looks of it, it appears most research in this area is
> identify a mechanism, find something that inhibits it, look for
> similar things to that inhibitor, and so forth. Am I right?

Yep. Fundamentally however you have to deal with the problem of
mutating DNA. A point I made perhaps 7+ years ago on one of the
aging newsgroups was as follows -- if ~30% of people die from cancer
and it takes only ~5 mutations in specific sensitive locations in
a subset of a few hundred tumor suppressor/promoter genes (those
regulating cell division) in a *single* cell in your body, then *what*
do you think is happening in all of the other genes in all of the cells
that *aren't* involved in getting cancer? [There is a really good
paper in this idea that I should write now that Nanomedicine is out
and most of the numbers are at my fingertips...]

There aren't going to be any *easy* mechanisms for inhibiting
DNA damage that don't involve some major genetic enhancements.
The best we might hope to obtain without some major re-engineering
is flipping the switches to reduce-the-damage/increase-the-repair
to levels found in children. That might slow the accumulation, but I
doubt it will stop it.

> A simulated aging cell could be used to more efficiently search for aging
> inhibitors and therapies, no?

Perhaps, but its way beyond our capabilities now.

NM [pg 115] - neuron volume: 14,000 microns^3, NM: [pg 384], molecular
volume of water (ignoring solutes & proteins since the density is not
hugely different): 0.0299 nm^3/molecule. If I'm doing the math right,
that looks to be about 4.7x10^14 atoms. Even a bacteria works out to
1.5x10^11 atoms. Given the max atomic level simulations now are at
a billion atoms, if we assume a generous Moore's Law that hits no
bumps providing a doubling every year, that means you don't get capacity
for bacteria simulations until 2007 and neuron cell simulations until
around 2018. The "Blue Gene" machine from IBM might speed this up
a little but we are still up against the wall of computational limits.

However, the nice thing about this, is that since the code exists for
modeling very precise radiation hazards and one would expect the
free radical effects to be accounted for in the cell model, we will
be able to model very accurately how and where the DNA is being damaged
*and* test various interventions.

Then finally, we just might settle the entire damn anti-oxidant supplement
debate once and for all.


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