Different cells, Different mechanisms

EdKrug at aol.com EdKrug at aol.com
Fri Aug 2 07:26:18 EST 1996


There seems to be a tacit assumption in the Aging research field that one
mechanism or one small constellation of mechanisms must account for decline
in function in all cells in all systems of any organism, the culminating
effect of which is organism death.  I contend that looking at aging from the
perspective of "Evolution of Longeviety"  offers some important insights into
the task of increasing healthy lifespan.

All that is essential in the evolution of apparently stable species-wide
fixed lifespan is that the different processes limiting lifespan have roughly
comparable times from start of timer to that point where sufficient
deterioration in function or structure has occured that life has become
untenably precarious or some cell has broken free of its internal and
external supervision and started  uninhibited replication.  Of course you
have to add in the individual variables of wear and tear, which is probably a
bigger factor for humans than the caged rat, and you get this coodinated
exhaustion of this multifacited "will to live" we call aging.

Telomer shortening doesn't have to account for deterioration in
non-replicating cells and culminating free radical damage doesn't have to
account for the deterioration in replicating cells.   They just have to have
run their course with about the same finish time.  Add in Advanced
Glycosylation End products and  one or two other other processes with the
same rate of decline and then apply them to thousands of interacting systems
in a complex multicellular organism and you get our problem in a nut shell.  

Using the "punctuated evolution" concept of Niles Eldredge, "Nature" has had
to "improve" one limiting factor to life span after another to take
multicellular organisms with a life span of one or two years and improve that
number up to 100 years.  There would be little selective advantage to fixing
any individual limitation more than perhaps 10% beyond the other limiting
factors.  The creation of a new SOD (superoxide dismutase) might increase
lifespan by 10%, but then some other factor becomes limiting and it too is
"fixed" to produce another 10% in life span.  The overall effect is that the
multiple processes tearing away at living systems have all been compensated
for at about comparable levels.   Thus you get families of enzymes, multiple
SODs, multiple receptors for the same hormone and so forth.  Each one is a
bit of fine tuning to the system given what is available.

To present this last concept as an image: consider a group of children
walking and  the group can go no faster than the slowest child.  You pick up
and carry or "fix" the slowest child and now the group can go faster, but
only as fast as the next slowest child.  Each act of picking up or feeding
another child so the group can go faster is a step in the punctuated
evolution.   Because this process has gone on for so many times the overall
difference in speed between the children is not great, but it is still real.
The more children in the group the more fixes needed.   The speed of the
group is the longeviety of an  organism.  Each fix, to be a fix, only has to
speed the slowest child up so that it is no longer last.    By way of
 adapting to the faster speed other changes take place within the group which
do not necessarly alter the group speed, they just advantage of the new nitch
in the world.

Given the multicipicity of interactions our trick is to not discard any fix
which improves some function but which doesn't address the current slowest
child and increase the lifespan but may address a later slowest child.

Sorry for the length.

Ed Krug, Ph.D.
Univ. of Colorado Health Sciences Center




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