From: Joao Magalhaes (joao.magalhaes@fundp.ac.be)
Date: Sat Dec 07 2002 - 07:23:45 MST
Hi!
At 10:26 06-12-2002 -0800, Robert wrote:
>I wouldn't say "aging" is programmed into the genes but genomes are
>programmed with other features that result in aging. So citing
>some other examples in this thread -- mice have hair and are primarily
>nocturnal animals so they do not really need extensive UV-damage DNA
>repair systems (compared with humans who are primarily active in the
>daytime). Lacking such systems might tend to increase their cancer rate
>(if say there are environmental toxins cause damages similar to UV
>radiation -- pure speculation) and thus tend to shorten their lifespans.
By saying aging is programmed into the genes I don't wish to imply that
aging evolved for a purpose. I don't see any evidence that aging in humans
or even mammals evolved for a purpose--as I point out in my Exp Ger paper.
I do see great differences in rate of aging amongst genetically similar
species, which makes me think rate of aging is a result of some small
alterations in the genetic program.
I've read your NHEJ-based theory before. I'll tell why I'm not convinced by
your theory and I'll tell you why I don't think free radicals cause aging
either. Life has billions of years on earth, having to face UV, background
nuclear radiation, free radicals, etc. I would say life had enough time to
develop protections against these common sources of damage and, equally
important, life had enough time to develop mechanisms to repair the
damage--DNA repair mechanisms are the perfect example. In other words, if a
yeast or a bacterial culture can divide eternally despite free radicals,
UV-damage, DNA mutations, etc., why assume--and most gerontologists
do--that our cells cannot cope with these processes? I think they do cope
and I think aging is caused by something else. One good evidence of this is
the huge amount of anti-oxidant protection in ALL--not just the ones that
live longer--but ALL mammals [See the papers by Sohal].
Now, if damage does not cause aging, then what does? Well, something goes
wrong in the genetic program. Hence aging is programmed into the genome,
though not intentionally. And I also don't think the program gets
corrupted. Why not? I've told you--Robert--before: clones. If there were a
widespread accumulation of somatic mutations in cells, we wouldn't be able
to clones so many animals--namely mice who have lots of cancer. That's why
I think the accumulation of damage as we grow older is epigenetic; I think
aging results from some sort of misregulation of the genetic program; the
expression of genes goes wrong with time. Since we're both programers, I'll
put my arguments in a programer's way: I don't think the program itself
changes much during aging; I think the program is bugged in some way that
the procedures and functions get out of control with time. Now, I have no
idea what genes might be involved, apart from perhaps the Werner protein.
Yet I think the key to understanding aging will be to understand the
transcriptional regulation of mammals.
Finally, you can argue that the soma of multicellular organisms lost some
protection against damaging agents and this causes aging. I mean, there are
papers correlating the resistance to stress with longevity in
mammals--though I don't think yeast H2O2 resistance is superior to that of
a human cell. It could be and I keep my mind open to such possibility, but
when I work with cells taken from a patient with Werner's syndrome, I see
that these cells are less resistant to stress than normal cells. What this
tells me is that one gene involved in DNA metabolism can make cells and
organisms less resistant to several forms of stress and thus shows how
multiple stress resistance might be a consequence, not a cause of longevity.
Anyway, I've been thinking of writing something along these lines and I
could use some comments.
All the best.
Joao
This archive was generated by hypermail 2.1.5 : Wed Jan 15 2003 - 17:58:36 MST