What is the cause of insulin resistance in the elderly?

Hang-Jun Jang iam at chollian.net
Sun Mar 22 12:32:39 EST 1998

Thanks Tom for posting valuable articles on possible mechanism to remove preformed
AGEs in vivo.

I'd like to point out two important facts in articles. First, AGEs in experiment are
all blood borne molecules that are unfixed to tissues as they are administered
intravenously. Second, AGEs are eliminated by two organs - liver and kidney.

Let's go back to the realities of life. Most of AGE modified molecules are fixed
ones or ones that turn over quite slowly, such as collagen molecules in blood
vessels and glomerular basement membranes, which are also major complicated tissues
in diabetes mellitus and probably glucose intolerance in the elderly. In this case,
most AGEs are not in blood, thus, they can't have access to liver and kidney. how
body eliminates such AGEs? I have a hunch that body might try to get rid of them by
immune mechanism because AGEs are known to be immunogenic. This fact is very
important! Let me quote a good explanation about this. " AGEs bind to receptors on
many cell types - endothelium, monocytes, macrophages, lymphocytes, and mesangial
cells. Binding induces a variety of biologic activities, including monocyte
emigration; release of cytokines and growth factors from macrophages; increased
endothelium permeability; increased procoagulant activities on endothelial cells and
macrophages; and enhanced proliferation of and synthesis of extracellular matrix by
fibroblasts and smooth muscles. Robbins PATHOLOGIC BASIS OF DISEASE, 5th edition
p917, ISBN 0-7216-5032-5 "

My hypothesis is as follows: These immune reactions might be quite harmful to
surrounding tissues. For example, they might cause fibrosis, autoimmune reaction,
programmed cell death of nondividing cells or even acceleration of cell division,
and accumulation of excessive extracellular matrix, etc. What if this mechanism
apply to the accumulated AGEs in the brain? Alzheimer's disease might occur. What if
in blood vessels? atherosclerosis, What if in kidney? Fibrosis of kideny and chronic
renal failure. What if in synovial membrane? Rheumatoid arthritis, What if in
hypothalumus? Neuroendorine disturbances and mood disorders in the elderly and so
forth.  I don't think that bodily defense mechanisms to remove them declines with
age, rather I think that miserable consequences of aging occur as a result of those
defense mechanisms. I call this idea "Paradox of Immune Reaction against AGEs".

My hypothesis sounds like an example of "antagonistic pleiotropy theory of aging.
What miserable beings we are! God created imperfect human body? The evolution of man
is under way! Hey, Hang-Jun, Can you be more patient and wait 10 billion years? No,
I can't. How about yourself? Let's do research hard.

Best Regards
Hang-Jun Jang

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