Re: Re : AGING: "Researchers Find Evidence Of Aging System That May Promote Long Life"

From: Alex Future Bokov (
Date: Thu Apr 12 2001 - 02:43:14 MDT


On Wed, 11 Apr 2001, Joao Pedro de Magalhaes wrote:

> 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

In theory there shouldn't be a selective advantage to pre-programmed
aging. Good example with the salmon, though... next chance I get to
corner an experienced gerontologist and foist that question on them,
I will do so and report back with the results. :-)

> 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.

Thanks for pointing this out to me. I'll need to read more about
sexual maturation in mice before I can form an opinion. If you happen
to have any references, or even partly-remembered names of authors or
paper titles, I'd be grateful. Either way, when I find out more about
this, I'll follow up.

> 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).

I agree with that. What causes different lifespans is how well an
organism resists these deleterious processes. The ultimate control
must be genetic-- since all species are exposed to free radicals, UV
light, etc. The CR effect is believed to be an evolutionary adaptation
to famine (an animal's fertility gets down-regulated and maintenance
mechanisms get up-regulated for the duration of the famine). If we can
figure out what key genes get triggered by CR and activate them
independently of CR, that will be a significant advance.

> >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

I'm not sure I understand. Do you mean if you feed mice a higher calorie
diet than they would ordinarily eat? Or do you mean if you take CR mice
and put them on a normal diet, thus making them no longer CR?

> 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.

"Atrophies" implies pathological processes, and this is not the case
in CR animals. They have less fat, and lower muscle mass, but no
degeneration. I'll need to do some lit searching to check whether they
exhibit lower activity or retarded development. The fact that they are
smaller and weaker doesn't automatically mean they are less
active. Lower temperature is not the same thing as lower metabolic
rate-- metabolic rate is measured as oxygen consumption per gram body

> 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?)

Ability to learn a maze, ability to remember where an underwater
platform is when they can't beneath the water they're swimming in, how
quickly they learn to avoid a situation where they get an electric
shock... there are dozens of very creative intelligence tests for
mice. It is of course debatable how any of these map to human
intelligence. I can tell you from personal experience that CR *can*
have negative psychological effects: depression and anxiety. This
could result in lowered functional intelligence. The problems went
away when I went back to a normal diet.

Remember, though, the goal is learning to reproduce the improved
oxidative stress response and improved repair mechanisms induced by CR
without actually undergoing CR.

Are you interested in aging research? If so, good for you-- it's a
crucial question as far as health is concerned, and interesting
from a theoretical point of view as well.


- --

Gore Wackenhut IRS
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