Free radicals and aging

EdKrug at aol.com EdKrug at aol.com
Wed Jul 10 14:19:25 EST 1996


Hello David Cassarino
     In answer to your question, presented below, threre are three points I
want to bring up for consideration.
     1.  Free radical scavangers may reduce but they do not eliminate totally
free radicals residing outside of tightly coupled reactions.  In a lab here
at the Univ. of  Colorado Health Sciences Center has been measuring in vitro
free radical damage as evidenced in the accumulation of lipofuscin-like
material.  He has been able to reduce the rate of accumulation by no more
than about 30% with all the interventions permitted in vitro.  Applying this
concept to the whole organism it becomes relavant to ask "What percentage of
the free radical damage is prevented by antioxidants?"   

     2.  Point one above is too simplistic in that even single cell organisms
consist of many compartments from which free radicals can be generated and in
which damage can accumulate.  Additionally, the different free radical
scavangers do not necessarly distribute uniformly throughout the whole
organism.  The cataloging of all the sources of free radicals and there
relative contribution to the total burden needs to be achieved, first in the
steady state and then the acute conditions with elevated free radical
generation, such as exhaustive exercise.    As an aside, would the levels of
antioxidants adequate in steady state life still be adequate in conditions of
elevated free radical generation?   I am afraid that there is much yet to be
done before we even know if the whole question has been asked, let alone
answered.

     3.  Free radicals are undoubtedly important but, in the evolution of
increasingly complex organisms the systems which limited life span in one
system may not have been abandoned or resolved as that organism evolved into
a different species.  Since Nature is the ultimate concervative it is
probable that some of the limitations of life span in earlier species are
still active in later ones.  Add to that the new threats to life span faced
by the later species and you have a many layer problem.  Consequently the I
suggest that we are not looking at an "either/or" situation but an "and"
situation.  We have:
      -accumulation of free radical damage
      -loss of cell numbers due to reaching their Hayflick number or
teleomere depletion
      -accumulation of simple wear and tear with "not just like new" type
repair
      -completion of the growth clock with a subsequent decline in growth
hormones and thymus activity
      -completion of the reproductive clock with concomitant loss of
reproductive hormones
       -steady and episotic accumulation of nonenzymatic glycosylation of
 multiple targets
       -gross abuse of the organism with poor choices in present time such as
excesses in food, alcohol, fat, smoking and more
      -irreversable "hits" taken from just living, such as intake of heavy
metals, chlorinated organic compounds, uv irridation and probably more.

     That is to say that achieving a fruit fly with ten times normal life
span should provide information useful for humans, humans have additional
life span limiting circumstances not faced by the fruit fly.  

     All that said, I contend that the fact that antioxidants can extend mean
life span indicates that they are part of picture.  As the free radical
component of senesence gets resolved the mist will lift and the remaining
factors will be seen more clearly.  I anticipate that this process will have
to be repeated a number of times.

     I hope this helps.

"The Devil (or GOD) is in the details"
"Life is what happens while we are getting ready"

Edward C. Krug, Ph.D.                           
Dept. of Infectious Diseases          
Univ. of Colorado Health Sciences Center
Denver, Colorado

<snip> 
""I have been reading a bit on the putative role of free radicals
in aging, and I'm wondering what others think about the
proposal that free radicals and oxidative damage are a
significant cause of aging?""

""Although it is clear that these factors are involved in such
pathologies as ischemic heart injury, autoimmune diseases, and
neurodegenerative diseases, it is not certain if they just
contribute to aging or are actually causative.""

""I think it's very interesting that in calorie-restricted
animals, the levels of free radical scavenging enzymes like SOD
and GPX are elevated, and that mice clones overexpressing SOD
have prolonged life spans.  The theory is that these enzymes,
and others like GSH-RD and catalase are protecting the organism
from oxidative damage to DNA, prots, lipids, etc., which
normally => aging and cell death.  
Arguing against the free radicals/aging theory are experiments
showing only an increased mean but not MAXIMUM life span in
animals fed antioxidants like Vits A, C, E, Se, etc.""

""I would really be interested in hearing others' opinions on
this topic.""

""David S. Cassarino              "The mind is not a vessel to be filled
MSTP, Neuroscience 2nd Year          but a fire to be kindled."
              
UVA School of Medicine                   -Plutarch
dsc9w at virginia.edu  ""





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