What is the cause of insulin resistance in the elderly?

Tom Matthews tmatth at netcom.ca
Sun Mar 22 22:27:22 EST 1998

Hang-Jun Jang wrote:

>> 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.

I haven't got any real argument with this at all.
It seems very reasonable and I agree that they are
likely a major accumulative cause of aging diseases.
I would like to know what exactly are the directions
that you propose for research to solve this problem?

In addition, not only can we not wait 10 billion years,
but many of us cannot wait until the research you propose
generates solutions. The short term answer is to keep
blood glucose to the lowest possible values one can be
healthy with (the chief proven method of doing this is
calorie restriction), to take a number of supplements
which prevent the formation of AGE's by different
mechanisms, and to do research to find other drugs which
prevent AGE formation and still others which reverse,
metabolize or otherwise eliminate them.

Tom Matthews
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