From: Joao Magalhaes (jpnitya@skynet.be)
Date: Fri Jul 26 2002 - 04:12:24 MDT
Hi!
At 22:47 25-07-2002 -0700, Robert wrote:
>It is going to take "a thousand cuts" to solve aging. The
>trick is to determine which cuts buy us the most and how
>do we develop solutions to them sooner rather than later.
I disagree. Not only I think many theories of aging will be proven wrong in
the future as I don't think that many deleterious processes cause aging.
Across different mammals we see an enormous variety in aging phenotypes and
in the rate of aging. Yet we are genetically close to other mammals. For
example, we have about 97% homology with mice and they age a lot faster
than us. In fact, I have an article submitted for publication regarding the
complexity of aging. I'll warn you when it's published. In a nutshell, my
arguments for a "fundamental cause of aging" are: progeroid syndromes such
as Werner's syndrome, CR, comparisons between mammals and between primates,
and life-extension by single genes such as p66.
>Fine. Perhaps a different way to think about it is that
>you may have many puzzles. If you have a piece that doesn't
>appear to fit in the puzzle you are working on, it may be that
>it actually belongs to a different puzzle.
Or it may be that my puzzle is part of another puzzle, a more accurate
puzzle. We'll see, but I have to start somewhere.
>I need to go back and review this work in detail to see what the
>precise details of the experiments were. But from my perspective
>it is unlikely that one would see an increase in defective proteins.
>Proteins that do not fold properly get degraded. What one would see
>is an decrease in "effective" protein synthesis per unit of energy
>consumed.
I read this in Strehler's book -- p. 293 -- and he quotes papers in the
60's and 70's, which I don't have. You're right, they don't see an increase
in defective proteins. I went to check it and what Strehler argues is that:
"Because some of the abnormal amino acids incorporated into proteins should
be incorporated into key sites of enzymes involved in
transcription-translation, the absence of significant life-shortening by
these incorporated analogues is compelling evidence against the
Medvedev-Orgel error theory."
>There is a lot of work with the HPRT locus finding both micro and macro
>deletions. There is also a lot of work with transgenic mice with the
>lacZ and similar reporter genes finding that deletion type and frequency
>have organ specificity (suggesting that the puzzle for aging in one
>organ may not be the same as the puzzle for aging in a different organ).
I'll be very surprised if there are different puzzles of aging for
different organs. Haseltine, the CEO of Human Genome Sciences, thinks the
way to tackle aging is to look at one organ at a time; he doesn't believe
in a "fundamental cause of aging". He's wrong. I don't advocate that aging
occurs all the same in all organs; even if the causes of aging are the same
for all organs, different tissues, different cells react differently to
deleterious processes. Yet I defend a fundamental cause of aging, and I
think there might be an organ serving as timekeeper. (Finch thinks it's the
brain; I'm not sure but I don't think it's impossible.) Of course I may be
wrong. "Prove me wrong, I might learn something."
Best wishes.
PS: Sorry if I sometimes send double posts to ExI but I'm having some
problems with my mail server.
--- Joao Magalhaes (joao.magalhaes@fundp.ac.be) IMPORTANT: MY MAIL SERVER IS NOT 100% RELIABLE. IF YOU EXPECT A RESPONSE FROM ME AND I DON'T REPLY WITHIN TWO WEEKS, PLEASE E-MAIL ME AGAIN. Website on Aging: http://www.senescence.info Reason's Triumph: http://www.jpreason.com
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