From: Robert J. Bradbury (bradbury@aeiveos.com)
Date: Sat Apr 19 2003 - 07:24:07 MDT
On Sat, 19 Apr 2003, Reason wrote:
> It seems to be claiming that if you cut out 1 1/2 amino acids of the normal
> spread of amino acids in rat food, you get long-lived rats. Can the people
> on the list who are way far more knowledgable than me about such things
> weigh in with whys and wherefores?
If you dig really deep into the literature (and I mean *really* deep)
you will find that restriction of some of the essential amino acids
(i.e. those that cannot be synthesized) cause an up-regulation of
protein recycling. As I recall there are multiple pathways that
may be involved (which makes sense from a biochemical standpoint).
The effect may also have some species specificity because I doubt
that species are likely to encounter the same amino acid shortages
given the variety of diets (of say mice/rats vs. humans).
The working hypothesis that others (and I) have had is that if
you increase protein recycling one gets a greater ratio of
"new" proteins vs. "old" proteins. The new proteins are less
damaged than the old proteins (from say oxidative or deamidation
damage) and thus function more reliably/efficiently. An increase in
the protein turnover rate may also cause proteins to be broken
down before they accumulate sufficient damage that the normal
recycling mechanisms will not work and they end up accumulating
as lipofuscin.
For more information you want to do a PubMed search on
"Cuervo AM" and/or "Dice JF".
Its also starting to become clear that there are "molecular clocks"
that determine the protein recycling rate -- see:
http://www.deamidation.org/
It seems highly unlikely (at least to me) that the clock timings are
setup optimally to recycle proteins as the protein recycling
machinery becomes less efficient due to it being blocked by
materials it is less able to recycle (e.g. lipofuscin).
This would be a classic case of antagonistic pleiotropy --
i.e. you don't want to recycle proteins too fast at a young
age because it wastes energy but when you get older and the
recycling machinery is less efficient the timings are too
slow to maintain the majority of proteins in an optimal state.
Is this "common knowledge" within the aging research community?
I can only state that I was at a lecture by Steve Austad, who
I consider to be a leading aging researcher, last week and asked
him whether he was aware of the molecular clock data.
The answer was "No".
I suppose that is one reason why one asks the ExI list...
Robert
This archive was generated by hypermail 2.1.5 : Sat Apr 19 2003 - 07:34:54 MDT