What is the cause of insulin resistance in the elderly?

Hang-Jun Jang iam at chollian.net
Mon Mar 16 13:24:46 EST 1998

> > This viewpoint is also right, but in the case of advanced glycation
> > end products, the cause is apparently plasma glucose. Insulin
> > resistance augments the bad effects of AGE products.
> But this doesn't refute my point. The real question is what causes
> insulin resistance and leads to higher blood glucose with age. The
> answer to that is one of the more "fundamental" causes that I am talking
> about.

> In addition, we can simply remove all plasma glucose. We currently have
> mechanisms for removing/repairing/undoing glycation. What is the level
> of blood glucose for which those mechanisms can keep up and why do those
> mechanisms decline with age.

Dear Tom, I am not going to refute your point. As I've already said to you,
your point is right. I just want to make my opinion more clear for you and
other readers. As far as I know, early glycosylation products are
reversible, but if once formed, advanced glycosylation end products(AGEs)
are not reversible, which accumulate over the life-time in interstitial
tissue and blood vessel walls. Aminoguanidine and some vitamins such as
thiamine pyrophosphate can prevent Amadori products from converting into
AGEs. In that case of diabetes mellitus, this adverse effects of AGEs are
just more accelerated than in old nondiabetics with mild insulin
resistance.  I speculate that even nomal level of glucose can contribute to
the accumulation of AGEs in tissues with advanced age. The degree of
glycosylation is directly related to the level of blood glucose. It is
impossible to undo preformed AGEs in vivo at present. If somone find out how
to remove it, the Nobel prize for medicine must be awarded to him or her. It
is valid that glucose 'itself' is a cause of AGEs unless there exits a
certain mechanism to undo preformed AGEs in our bodies.  This is a logic
easy to understand. As long as our bodies use glucose as a major fuel, AGEs
will accumulate with time.It might be the cost of using glucose as a fuel.
'Glucose Toxicity' are now being recognized as a important concept in
understanding pathophysiology of diabetic complications. Now I re-emphasize
that glucose is a primary cause of AGEs, which might be a underlying
mechanism of insulin resistance in the elderly. It's our task to elucidate
how glucose toxicity  causes insulin resistance. Tom, My hypothesis haven't
been tested yet. I am looking forward to more promising results in journals.
You said we currently have mechanisms for removing/repairing/undoing
glycation. Could you let me know them?

> >      It is highly unlikely that any of the fundamental causes of
> >      aging are
> >      "everyday ones".
> > This opinion can be true and can be false. Fundamental causes sound
> > like mechanisms of diseses' process or pathogenesis. The meanings of
> > causes or etiologies are different from those of mechanisms or
> > pathogenesis. I mean a cause is  a  'TRIGGERING' factor. I sometimes
> > think over the relation between genes and environments. Genes determin
> > some predispositions to a certain disease. Most of doctors agree that
> > many causes of diseases are environment factors arised from life
> > style. Eating is a very important component of life style. Everyday
> > ones are things we have to do everyday to survive.
> However, except for calorie restriction, none of those "everyday ones"
> have been shown to consistently increase the fundamental rate of aging,
> ie. to increase the maximum lifespan of a species.
> > We have to pay more
> > attention to the effect of calorie restriction on longevity. Every
> > mouse eats food that is 'everyday one' and if some parameters of
> > everyday ones, such as amount of food, are modified, their longevity
> > is significantly changed. It is,therefore, likely that everyday ones
> > can be very importan or fundamental causes of aging process.
> I disagree. For individual health and living up to the maximum species
> lifespan, I agree that "everyday" lifestyle variables are important.
> However, there is no evidence that they will effect maximum species
> lifespan which is what a fundamental modification of the causes of aging
> would do.

My opinion is quite speculative, not a confirmed fact. My intention is to
arouse researchers' attention to everyday ones. Very important variables
often tend to be ignored.  It's not important wheather you agree or
disagree. That's not my point.  I just want to give biogerontologists a
chance to think that everyday ones might be  worthwhile variables to prevent

aging process. It couldn't be better to easily slow down aging process by
modifying everyday ones without much money, rather than to take expensive
anti-aging drugs in a lifetime. That's all.

Best Regards
Hang-Jun Jang

If I have time to spare, I will write about Nonenzymatic glycosylation. I am
looking forward to further disscusions about this matter. Good luck to you.

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