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Antiaging Research Priorities [was Re: Major Criticisms of The

James james at nospam.com
Thu Sep 17 12:48:37 EST 1998


> First I've seen numerous posts, (but not from Tom), that state that CR is one
> of the very few methods of extending any organisms life span.  This is
> patently not the case.  The appropriate way to phrase this phenomena is that
> "Caloric restriction has been demonstrated to retard aging processes and
> extend *maximal* life span in some species."
>
> While CR mice do live longer than mice whose diet is not restricted they live
> no longer than than other mice on CR.  Their life span has not been increased
> by CR only their life expectancy has been increased.

I know someone already said "huh?" to this, and I'd like to second the motion.
I'm not trying to be whatever...  I really have no idea what this is supposed to
mean.  I assume that it has something to do with an average versus maximum age
argument that you are trying to make.

Regardless, I do not believe that you are correct.  Caloric restriction has been
shown to increase both average and maximal lifespan (see Yu et al. 1990, Yu et
al. 1982, Sohal R et al. 1996, Weindruch R, 1996, etc.)  A rough calculation from
looking at the graph in the Yu paper (which used 115 rats in each group) shows
about a 37% increase in maximum lifespan and more like 50% increase in average
life span.  So if you're saying that everyone has changed their minds in the past
two years please provide references.

> This relegates this research to the same class as vaccines, antibiotics,
> hormonal replacement and dietary supplements. It is valid research and could
> possibly achieve some significant increases in human life expectancy but has
> little if any relation to extending the human life span.

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 in
humans.  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.

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."  Is anyone thinking that?  Wrong.  Because in those extra 20 to 40 years
that caloric restriction will allow you, if history is any indication, you will
have time to witness (and take advantage of) vast scientific progress that we
cannot even guess at right now.  I would say that if you knew right now that you
could live to be 120 with caloric restriction, your prospects for living well
beyond that (by taking advantage of the next 50-100 years of scientific
advancement) are pretty good.  Very good in fact.  Look at where we were 50 years
ago.  We didn't know what a restriction enzyme was.  We had only recently
discovered the structure of DNA.  And personal computers we not due to exist for
30 years.  50 years is like night and day in science.  And if you happen to be
fairly young and might expect to have almost 100 years from today...

> Dr. E.J. Masoro, a major researcher in the field of CR at The University of
> Texas Health Science Center at San Antonio, has suggested two possible
> mechanisms. The first is "the altered metabolic characteristics of glucose
> fuel use and of oxidative metabolism" and the second "relates to the enhanced
> ability of the rodents restricted in food intake to cope with challenges,
> which in turn has been linked to the glucocorticoid system and to the
> heat-shock protein system".
>
> Any suggestions on how to proceed?

Yep.  As I have already mentioned let's stop shooting in the dark and find out
exactly what genes are being up or down regulated by caloric restriction.  We can
do it now (using DNA chip technology), with the incomplete genome sequence (which
means we will probably have to do it again later) and at least that will give us
something to work with for the next 5 years of so until we have the complete
sequence.

A complete DNA chip center with a chip maker, chip reader, oligo synthesizer (or
more likely you would buy the oligos for the genes or ESTs) can be setup for
about $250,000 plus reagents (and maybe licensing costs for the ESTs).  You could
do it for cheaper with a commercial setup like the machines Affymetrix makes, but
you are then limited to the chips that they can supply, which would be inadequate
at this point in time.  That's pretty expensive for a single non-profit lab, but
it's peanuts for a big company.   Which probably means that this is already being
done by some of the big drug companies.  But of course they are not going to
release their data, so we need to duplicate the work.





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