I'll toss a couple of cents worth in on this discussion.
The claims made by Hayflick are based on work done by
James Fries. The relevant references are contained in the list:
http://www.aeiveos.com/Aging/Authors/fries-jf/
The comments regarding why we age and some of the things
we need to focus on are pretty much on the money. People
on the list should pat themselves on the back since this
is stuff the average practicing physician or molecular
biologist will not get right.
I'm dubious regarding what the study of tortises might
tell us due to the fact that they don't maintain a high
body temperature constantly, so their rate of damage
accumulation may be lower. You want to study elephants,
whales and long-lived birds. Ultimately they have each
solved different parts of the problem in different ways.
(Of course going back at some point and studying tortises
will be useful, but it isn't something likely to contribute
to the retardation of human aging soon.)
The topic is getting more discussion, from the bet being
made between Austad and Olshansky, see:
http://www.the-scientist.com/yr2001/feb/mccann_p8_010205.html
[Use something like nobody@nowhere.com if you don't want to
cough up a real password...]
They are both wrong, but they don't understand the technologies
we will have, so they can be excused.
The topic is even getting, "serious, conservative" scientists like
Francis Collins (director of the NHGRI @ NIH) to forsee:
"Ten years after that, by 2030 we will have cataloged all the
genes invoolved in ageing... and clinical trials to extend
the human lifespan could be underway. A full computer model
of the human cell will replace many lab experiments. And
complete genomic sequencing of the individual will be routine,
costing less than $1,000."
also
"There'll be serious debate about the notion of taking charge of
our own evolution. It'll be a very noisy and vigorous debate."
- Genetic Engineering News 21(3):22, Feb 1, 2001
Of course, Dr. Collis is a bit pessimistic with regard to when
we will understand the genes that directly "contribute" to aging
(those that are plieotropic in nature), but perhaps optimistic
with regard to our understanding those errors in the genetic
program that are simply "missing" (e.g. the anti-cancer program
that whales or elephants might possess).
A reporter from Italy asked Robert Freitas about the implications of
the publishing of the genome information on "nanomedicine" and he
forwarded part of his commentary to me. I subsequently commented
to the reporter, regarding the "pre-diamondoid" bio-nanotech path
as follows:
> Here is the logical progression of what will develop:
> (a) We will begin to understand the function of all of the genes.
> (b) We will associate thousands of known human genetic defects
> with single or a few interacting genes.
> (c) We will develop gene therapies (or drugs) that can mitigate
> or correct those defects, first for single genes, then for
> multiple genes. (Note the tradeoffs -- drugs you may have
> to take the rest of your life, while a gene therapy may
> provide a "permanent" fix, similar to a vaccine).
> (d) We will understand the defects in the genetic program that
> result in aging, and develop interventions in those.
> (e) We will develop an entirely new discipline of "genome
> engineering" that allows us to design machines that can
> assemble themselves (like plants) that do everything from
> manufacture fuel to cleanup the environment.
> (f) We will develop cells with artificial genomes that allow
> us to grow (inexpensively!) replacement organs that
> can replace old and worn out organs.
> (g) We may be able to get to the point where we have artificial
> genomes in cells that can be put into your body that gradually
> grow into new organs while removing the tissue of the old organ.
(The "We" is the biomedical research community in its entirety.)
I think we get (a-f) at an increasing rate over the next 20 years.
With regard to (g), I put that as the hardest thing to accomplish
with the tools biology provides for us. Though the functions needed
for this are found in Nature, they are rarely assembled into
a functional system that works this way (unless you want to cite
something like the caterpillar turning into a butterfly).
Now, I'll give you one example of the synergism I expect to see
over the next decade.
>From Nature Genetics 27:209-217, T. LaVaute et al, "Targeted
deletion of the gene encoding iron regulatory protein-2 causes
misregulation of iron metabolism and neurodegenerative disease
in mice."
The bottom line of this article is -- lose control of your iron
and you get neurodegeneration. So a single gene knockout in mice
gives us critical insights into aspects of the genetic program
where we would want to look for polymorphisms, for "stricter" or
"relaxed" iron regulation, that contribute to neural degeneration.
Using the millions of polymorphisms that are now known will allow
organizations with large patient populations (e.g. HMOs) to construct
databases of genomic information to rapidly associate the clinical
health with probable causes. This then leads to mitigating therapies
(e.g. chelation). Ultimately one may want to get to the point where
we are genetically engineered to manufacture our own chelating agents
if our iron levels get too high. (For example, if garlic turns out
to be a natural chelator, one borrows the genetic pathway for that
and figures out how to put it into humans... Interesting concept,
you are always able to tell when the 100+ people walk into the room...).
Now, I can't tell whether we have the resources to knock out all
30,000 genes (or the 140,000 down-stream splice variants), but
I suspect that most of the major genes that people suspect to
be involved in aging (oxidative stress, iron regulation, glycosylation
lipofuscin accumulation, telomere shortening, cell scenescence,
DNA damage inducing apoptosis, DNA repair, etc.) are going to get
*lots* of attention. We are going to know a lot in 10 years that
we don't have clues about now.
Robert
This archive was generated by hypermail 2b30 : Mon May 28 2001 - 09:56:46 MDT