Antiaging Research Priorities [was Re: Major Criticisms of The

James james at nospam.com
Fri Sep 18 13:17:52 EST 1998


> Let me spell it out.  Mice have a genetically fixed life span, probably
> determined by the short telomeric length on some chromosomes, (I threw that
> in just to keep Tom happy:-).
>
> The ages shown below are approximations and vary significantly depending on
> the type of mice studied but the relationships between the ages demonstrate
> my analysis.
>
> Laboratory mice fed ad libitum or an unrestricted diet live approx. 2.5 years
>
> CR mice on a diet at 60% of ad libitum live approx. 3.5 years.
>
> Wild mice who eat when they can and often go without food live approx. 3.0
> years.
>
> Since no mice live longer than 3.5 years then the genetically determined
> *maximal* life span is 3.5 years.

OK, now I see what you are saying.  It's all semantics.  You want to make maximum
lifespan mean "maximum possible lifespan without genetic modification."  It's an
interesting thought, but that isn't how the term is normally used and that just
causes a lot of confusion.  I would ask that we use "maximum lifespan" to mean
"maximum lifespan observed in the wild without researcher intervention".  There
is no point in using terminology in a manner that differs from the scientific
community at large.  That just hampers clear communicaiton.

[snip]

> >And even if you were correct and caloric restriction only increased average
> >life span, placing a high priority on the research would still be 100%
> >justified. There is a very large difference in average life span versus
> >maximum life span inhumans.  For round numbers let's use 80 for average
> >lifespan and 120 for maximum lifespan.  That means that the worst case
> >scenario is that caloric restriction gives you another 20-40 years (on
> >average), instead of allowing you to live beyond 120.
>
> Possibly, assuming that the adaptive reponse seen in CR mice is at all
> applicable to the way that humans respond to a restricted diet.  This has not
> been demonstrated by the research to date.

Not true.  I posted preliminary information on primate studies going on at NIH a
while back.  To quickly summarize: The study has not been ongoing long enough to
have mortality data, but many aging biomarkers show that the effect on primates
is exactly what we see in mice and rats.  If you want to say that primate data is
not applicable to humans I suppose you are free to have that opinon, but I don't
buy it.

> >Perhaps you are saying "But a life expectancy of 100 to 120 years in not
> >satisfactory to me, so I will research things that, while they may be much
> >less certain, have a chance of extending my life much more than caloric
> >restriction can."
>
> If this research, which has been going on for quite some time, showed promise
> that we could extend human life expectancy by 20 years or more I would be
> behind it 100%.  The results aren't there!  There's not even a suggestion
> that this research will achieve these results any time soon.

Completely untrue.  See above.


> Even the basic
> theory as to how or why it might work has not been established.

Somewhat untrue, but I do concur that it is very much a "black box" phenomenon at
this point.  So what?  It works.  You don't need to know the molecular basis to
reap the benefits if you want to practice CR right now.  On the other hand, if
you are referring to developing drugs that will mimic CR, of course we need to do
a lot more work.  But the problem is hardly, as you call it, "insurmountable".

> In mice it has
> not been effective in older mice

It is true that you derive more benefit form CR the earlier you start practicing
it (within limits?).  That gives us some interesting clues as to how it might
work right there.  So it's not perfect.  So someone who is 50 now might only
derive half the benefit from it that someone who it 30 would get.  So?  It's
still the best thing we have, we know it works (IMHO), and the benefits are
fairly substantial.

> the beneficial effects of CR have not been
> demonstrated on species closely related to mice let alone man and at best it
> will only improve quality of life.

What?  You'll have to explain that one.  I'm not aware of CR ever failing to be
demonstrated in mammals, and your statement that it will only improve quality of
life goes back to an argument of semantics.  If you are calling living for 100
years instead of 80 "only an improvement in the quality of life", I'll take that
improvement any day.

> I agree completely.  But lets work on something that has a chance of getting
> us there.

I submit that this is the best thing going in the near future.  See all comments
above.

I'd like to finish by saying that I don't work on CR, I don't do CR, I don't even
*like* CR because I know I won't be bothered to do it, and it doesn't satisfy my
sense of scientific aesthetics.  So if I'm biased in any way, it would be against
CR.  But you've got to face the facts here.  CR works.  It is the ONLY thing that
definitely works.  And it will be perfectly tractable to study in a molecular
sense within the next few years (if it is not being done already by private
companies).  Your comments like "But lets work on something that has a chance of
getting us there" are completely without merit.  If I had to bet my life (pun
intended) on whether we could find drugs to duplicate CR before we figure out the
whole telomerase story, cure cancer (without which telomerase is very risky), and
develop vectors that could introduce telomerase into every nook and cranny of an
adult human, it wouldn't even require any contemplation.

James





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