X-Message-Number: 10676
Date: Mon, 2 Nov 1998 08:10:07 -0500
From: Thomas Donaldson <>
Subject: CryoNet #10672 - #10675

To Brian Delaney:
First, thanks for the reference. 
Second, yes, there ARE short-lived strains of mouse. Many of them wree
specially bred to be subject to some condition, say cancer. Most people
who want to test the effect of a drug on lifespan do not use such 
mmice, for obvious reasons.

Moreover, the lifespans of different strains of mice, even those not
bred for some particular condition, do differ. You ask a cogent question
when you ask what the meaning is of an experiment on a RELATIVELY short-
lived strain which prolongs their lifespan. Since we will likely find 
genes which prolong mammalian lifespan, just like we've found such 
genes for other animals, it seems to me that (given that the strain 
involved is not bred to have a short life) we have good reasons to believe
that the drug works on aging. After all, we should not assume that all
people age at the same rate, or all mice. And in the absence of an 
experiment which FAILS to increase lifespan on a strain which has a 
longer lifespan, such experiments do suggest an effect on aging. (Yes,
I would applaud such an experiment, but we should be aware of our
assumptions here).

One thing to keep in mind is the actual lifespans of the different strains.
I have a reference to that, though it's not at my fingertips. I will give
you the reference the next time I get on Cryonet. 

If you actually read up on melatonin, you will discover that it is among
the drugs which may mimic CR, at least in some respects. The reason for
this is that CR retards changes in the pineal gland (which produces
melatonin), and thus with CR your melatonin remains relatively high.
Pierpaoli is far from the only person who has done lifespan experiments
with melatonin. There is a popular book which you might get which 
discusses these various issues, RJ Reiter and J Robinson, MELATONIN.
Furthermore, Pierpaoli has done a second type of experiment which is 
also of interest regarding melatonin: he and his collaborators 
transplanted pineal glands from young mice to older ones of the same
strain (often these strains have virtually no immune reaction to 
members of the same strain). This operation worked even better than 
giving the mice exogenous melatonin. Pierpaoli also tried melatonin on
more than one strain. Melatonin also shares one feature with L-Dopa:
if the dose is too high or given when the mouse is too young, it actually
SHORTENS lifespan. Pierpaoli has also written his own book on melatonin,
THE MELATONIN MIRACLE. This, too, deserves a read, ESPECIALLY if you
want to criticise his experiments. I will add that on reading his 
experiments, I checked the lifespans of the strains of mice he used.
Neither strain was especially short-lived, nor were they bred to be
subject to particular diseases. (I am exlicitly disagreeing with 
Steve Harris here, if that is what he claimed). 

As for working out the metabolic effects of CR, I am sure that there
are many. AS a way of finding out just why it works, that seems to me
to be a rather poor strategy, since it gives you no way at all to
choose between them. One interesting experiment (which might --- or might
not --- show that melatonin and CR are related) is to try CR on mice
which lack a pineal gland. Since some strains of mice also make 
melatonin elsewhere, you'd want to make sure that you don't do the
experiment on such a strain. Or perhaps you simply try using rats
instead. If the effect of CR is to keep production of melatonin at
young levels until relatively late in life, than mice without a pineal
gland (which make their melatonin there!) might show no effect at all
of CR. 

I note that you have given one reference. I will obtain and read it
with interest. 

Finally, you wonder about my motives. Basically I think that some drugs
do affect aging, and have behaved accordingly. I also think that these
drugs deserve more attention: we may find that some which SEEM at first
to affect aging don't change anything fundamental, while others do.
But that requires many more experiments. And I doubt very strongly that
CR is the only strategy available to us if we wish personally to delay
our aging. Not only that, but these drugs deserve just as close attention.

And just to tweak you, I'll point out that GH-3, the drug long ago
promoted by Anna Aslan, shows in her experiments with RATS a longer
maximum lifespan of treated rats than controls. (No, I don't take
GH-3. But the curve she got is still interesting).

			Best and long long life,

				Thomas Donaldson

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