X-Message-Number: 10663
Date: Sat, 31 Oct 1998 00:59:26 -0800
From: Brian Manning Delaney <>
Subject: Re: Calorie Restriction
References: <>

Alas, it looks as though it will be such a long time before I get
to the medical library that I'm just going to respond to a few CR
points somewhat half-assedly (that is to say, approximately
1/10-assedly, if I'm not being too generous with myself :)

First-in, first out order.

To Thomas Donaldson:

Thanks again for the reply

A quick recap, to make sure we're on the same track. We began
with my disagreement with your claim of October 12, in CryoNet
#10572 --

TD> However quite a number of studies (you should be
TD> able to find them yourself) show in animals that
TD> calorie restriction begun after puberty WILL
TD> increase lifespan. By not nearly as much, in
TD> fact by about as much as various drugs are
TD> claimed to increase lifespan. But the effect is
TD> still there.

I contended, and still contend, that there is no evidence to
claim that any aging intervention in adulthood comes even close
to the effect shown in adult CR studies. (I contend/ed further
that it's important to make this fact KNOWN to
life-extensionists!) Specifically, I claimed:

BMD> No drugs have shown an increase in maximum life
BMD> span in 1) repeated, 2) well-conducted studies,
BMD> with the _possible_ exception of deprenyl (merely
BMD> "possible" because I'm not yet convinced the
BMD> studies were well-conducted). The most important
BMD> criterion for "well-conducted" is controlling
BMD> for the effects of CR (which one or two of the
BMD> deprenyl studies did, though indirectly)

I've never seen anything to indicate that my claim is wrong. If
you, or anyone, think this statement is incorrect, please say so,
and why. Meanwhile -->

Curious to see what longevity studies might be out there that I
might have missed, I then dropped the "repeated" criterion, and
asked for citations of studies that fit the other criteria. You
cited five studies (Cryonet #10617). I am familiar with these.
None of these studies counts as well-conducted for the purposes
of showing an anti-aging effect, as I see it. (It has been a
while, though, since I've read the L-Dopa and dilantin studies.)

Since I haven't been able to refresh my memory on two of the
studies, please feel free to correct my brief comments below if
I've boned something.

The main point is: I don't recall that any of these studies
controlled for CR, aside from the HGH and melatonin studies.
(Comments on the HGH study will have to wait, comments on
melatonin studies are below.)

From your comments earlier I thought you agreed that one cannot
make conclusions about the effect of an intervention on the aging
process from a study that does not control for the effects of CR.
Perhaps you don't believe that. If so, I would want to know why.
(And if I'm disremembering, please let me know!)  I'm unaware of
any good aging researcher who today would agree with such a view,
but this, of course, doesn't mean all good researchers are right.
(But, for reasons alluded to earlier, I think they most certainly
are right.)

As is true of the CoQ-10 study you cite (as you noted), none of
these studies has been repeated. Moreover, attempts to repeat the
findings in the case of CoQ10 and L-dopa (at least), have not
shown an increase in maximum life span. (Raison d' tre of the
"repeatable" criterion.)

About the melatonin studies: The biggest problem here is that
short-lived (or ~medium-lived) strains were uised.
(Anti-contentiousness department: I'm not saying this means you
didn't produce an example of what I was asking about.)

It's important to stress that a short-lived strain of mouse is
not different from a long-lived strain in the way that chimps are
different from humans: healthy to the same degree, yet with a
faster running aging clock. Rather, they are different in the way
that, for example, people with familial hypercholesterolemia are
different from average humans: they are genetically predisposed
to die from _particular_ diseases at a much greater rate than
longer lived strains (there are arguably some exceptions to

If we conducted a vitamin E study using only people with familial
hypercholesterolemia, in both the control and experimental
groups, we quite likely would find an increase maximum life span
in the experimental group (and certainly in avg. life span). But
this would not enable us to say that vitamin E slows aging, even
in the people being studied (though people in a different
"strain" who happen to have high cholesterol might well live
longer if they take vitamin E).

Thus, we can't conclude from the melatonin studies that melatonin
slows aging (though I do think melatonin is the most promising
anti-aging regimen that we currently have, aside from CR)

> Not only that, but any serious attempt to work
> out how to prolong lifespans should hardly stop
> with CR. After all, compared to 1000 years, even
> a 50% lifespan increase is small. So where do we
> go then?

No argument from me here, obviously. We ultimately need to figure
out how to stop telomere-shortening, repair DNA (including
mtDNA), regenerate brain cells; and, eventually, increase our
cognitive capacity through artificial means, solve world hunger,
find a new star when ours burns out, understand what Plato meant
by "The Good," etc., etc. :)

But none of this is an argument against contemporary CR research,
or CR-advocacy.

In conclusion, I stand by my previous claim.

Further, I contend that life-extensionists who choose not to do
CR solely for the reason that they think there is evidence that
they can achieve the same results with something else are
mistaken, and need to be disabused of this view. (Again, there
are _plenty_ of other reasons not to want to do CR.)


Yesterday, in #10656, you wrote:

> (I'll add, too, that you have not disposed of
> the "developmental program" explanation simply
> by the observation that CR works after puberty.
> We develop after puberty, too. Some authors
> claim that even aging comes under that heading).

Well, if aging comes under the heading of development, then
saying that CR works by delaying development is the same as
saying that CR works by slowing aging, which isn't an explanation
of how CR slows aging, of course.

But you're right, there's more work to be done in understanding
how CR slows development, if that turns out to be the right way
to think about it. (It's not clear to me that it is the right way
to see it, however.)

> So here are some MORE suggestions, just to add
> to those I gave for  Jan Coetzee. We note that
> CR restriction causes the CR animal to have a
> variety of metabolic differences from a normal
> animal. You suggest, for instance, that improved
> glucose regulation plays an important role in
> the effects of CR. Well, the obvious experiment
> is to take a population of NON-calorie
> restricted animals and try with drugs (chromium
> picolinate comes to mind, but aminoguanidine is
> worth trying too.

It's been done.

> And a good search is likely to find still others).

Yes, they're being found, and being tested.

> Do these drugs produce similar effects to that of CR?

Nope, they don't increase maximum life span. Quite annoying. But
it does tell us that, if CR works by altering glucose regulation,
it doesn't do so in the way induced by the agents so far tested.

But there are more to be tested.

> If not, why not? Among other questions such a
> hypothesis suggests is simply that of finding
> the point at which the improved glucose
> regulation occurs [...]

Precisely. We know now that CR's effect isn't simply a matter of
lowering blood-glucose levels. (Though this is probably part of
the CR effect.)

> It may or may not be of interest here that
> chromium picolinate does cause an increase in
> lifespan.

Average life span, yes, in a couple of studies which didn't
control for CR. (In all the ones I've seen, where weight is
reported, the chrom. rodents weigh less than the controls. So
it's likely -- at least possibly -- a CR effect.)

> The aim of such an experiment is not just to
> decide that CR causes better regulation of
> glucose metabolism, but to work out in much more
> detail just how it does that.

Yup. It's being done. Who knows, we may have a CR-mimicking drug
sooner than some suspect.

> CR most certainly causes lots of metabolic
> changes. The only way to work out exactly which
> of these is primary and which is secondary is
> NOT to work only with CR mice, but instead to
> produce similar changes by other methods and see
> just what they do to the treated animals.

It's being done. In addition to glucose metabolism, immunological
alterations are being induced which might mimic one aspect of
CR's effects. And there are some people cutting out this and that
gland to see if the CR effect might either be induced without a
dietary change, or whether, without a particular hormone, the CR
effect cannot be produced at all, regardless of the institution
of an actual CR diet.

> Repeated repetition of CR experiments, in which
> some new variable is  measured, just isn't going
> to tell us very much at all.

Yup. Again, no one is doing this.


To Mike Perry:

The finding that CR induces amenorrhea in calorie-restricted
rodents is so well-established that it's hard to find anyone who
even mentions it anymore. I'll try to dig up some references,
later, though. Walford mentions this a few times in _The 120-Year
Diet_, if you happen to have that on your shelf.

Pardon typos,
Brian Manning Delaney
(No need to CC articles to me.)

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