From: Joao Pedro de Magalhaes (joao.magalhaes@fundp.ac.be)
Date: Wed Apr 11 2001 - 09:10:57 MDT
Hi!
You wrote:
>On Mon, 9 Apr 2001, Joao Pedro de Magalhaes wrote:
>> Until proven contrary, I maintain my opinion that caloric restriction or
>> other manipulations of organisms' energy -- such as this research -- slow
>> down aging by slowing down the rate at which the organism completes its
>> genetic program. Although this might lead to extensions in human lifespan,
>
>A genetic program for aging?
Forgive me for my computer analytical mind. I tend to see the DNA as a
computer program. After conception, the software starts to run aiming at
producing offspring. Aging can be either pre-programmed in the genetic
program (e.g. salmon) or a result of bugs whose damage accumulates as the
program runs (e.g. humans). CR mice can take twice as much time to reach
sexual maturity; therefore, CR does not only delay aging, it delays the
entire ontogeny -- i.e. the genetic program -- of an organism.
>What is meant by basic mechanisms?
Some might disagree, but I think that human aging is caused by some
deleterious process acting continually over time. Good examples are the
popular theories: free radicals, DNA or telomere damage, mitochondrial
damage, etc. Generally I call senescence to the basic mechanism of aging, to
the errors in the genetic program that cause our vulnerability to increase
with age (this excludes individual age-related diseases such as
farsighteness, which would develop with or without senescence).
>> aging. Finally, caloric restriction in animals (mice and monkeys) leads to
>> diminished body functions which are undesirable for a normal human being
>> (for instance, diminished physical abilities).
>
>Yes, except mice and rats do *not* show a decreased overall metabolic
>rate (per unit of body mass) under caloric restriction. Nor lessened
>activity. Nor lessened intelligence. The possibility is still open
>that the metabolic rate of individual organs or tissues is different
>under CR, with the whole body metabolic rate not significantly
>altered.
As you probably know, if you increase the caloric intake of mice, they live
the same. So, total energy consumption does not explain everything. You can
argue that perhaps CR forces the optimization of energetic pathways.
Alternatively, it would be fun if lower temperatures in CR animals somehow
lessen molecular damage. Now, if you had a normal development and a
decreased rate of aging under CR, I would be excited. Since everything is
slowed down and animals develop atrophies, at the moment (and I do not
discard future developments in the field), it tells us very little about
senescence. And the side-effects of CR remain undesirable: you wrote "Not
lessened activity" but the animals are smaller and have lower temperatures.
They can't practice exercise like normal animals! And if you apply this to
humans, most persons -- e.g. I -- will not accept it.
Thanks for the references. One question, how do they measure the
intelligence of mice? I ask this cause it's something I've been thinking
about (if CR generally leads to less muscles, why not smaller brains too?)
Best wishes.
---
Joao Pedro de Magalhaes
The University of Namur (FUNDP)
Unit of Cellular Biochemistry & Biology (URBC)
Rue de Bruxelles, 61. B-5000 Namur. Belgium.
Fax: + 32 81 724135
Phone: + 32 81 724133
Reason's Triumph: http://users.compaqnet.be/jpnitya/
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