Re: Cellular aging

From: Technotranscendence (
Date: Wed Jan 26 2000 - 08:16:08 MST

On Wednesday, January 26, 2000 6:09 AM Robert Bradbury wrote:
> > Also, cryobiology is not the only field I mentioned. Antiaging research
> > the other. What of that? If one can develop a good model of aging at
> > cellular or molecular level, then finding new ways to combat it would
> > 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.

I imagine so.

I also question whether gene expression is everything here. I know it's an
important part of understanding how life works. (In other words, spare me
the lecture on what genes do.:) But the narrow focus on it leaves out
everything else, don't you think? Another way of putting this: Is most
aging a failure of gene expression? (Using "failure" here to cover things
not working as they did when someone was young -- so that the failure of an
oncogene to express itself would not be considered a _failure_ in the abvoe

> 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
> 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.

We have a huge pool of aging people in the West... Even if they volunteer
for some of these tests, that would not cover the costs of the tests
themselves. How much do you think that cost would be now per person?

I wonder if the Life Extension Foundation has tried to make an outreach to
its members to gather statistics on them. That might help, since some of
them are already purchasing various blood tests as well as taking
supplements. (I'm assuming this because they sell the stuff.:) I don't
know how many people buy these blood tests.

I also assume that the medical establishments around the world maintain some
records of when they've done some of these tests. How much of that data is
up for grabs? How much of it can be purchased? What is its quality and the
follow up rates?

> > 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...]

I assume that DNA are constantly undergoing mutations anyway. Most of it,
and this is my guess borrowed from Kimura (the Neutral Theory of Selection
guy), is harmless or has no effect. At least, I bet it has no or little
effect in the short run. As we live longer, I would think that not only do
the mutations add up, but that some that would be harmless at one age might
not be so at another. I'm just speculating here and don't have that much
knowledge of the field. (So forgive me if I sound more like a drunk at the
corner tavern, then a biology student.:)

> 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.

My hope is you live a little longer, the science understands more, the
technology gets better at antiaging, and repeat.:)

> > A simulated aging cell could be used to more efficiently search for
> > 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.

I was not aware of the exact numbers, though thought they would look
daunting. I'm sure we can make simplifying assumptions here. For instance,
if we can model just one part of the cell membrane, we might come to a
better understanding of freezing damage at that site. Surely, it will not
be an exact fit, but the map is never the road, right? This doesn't stop
people from driving from LA to NYC.:)

> 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.

I was unaware some modeling has been done in this area. That is good to
hear. Perhaps, it's just a matter of tweaking an existing modeling to suit
our needs. Who is doing the aforementioned modeling?

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

And open new, more productive lines of antiaging and cryobiology research.

Daniel Ust
    Your center for tar water information is:

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