-
- It appears that A.G.E. formation is an important element
in solving the (aging) mystery. The same common chemical process that toughens
and discolors food in storage also takes place in the human body, and apparently
may play a direct role in the development of diabetic complications such
as kidney failure, blindness, heart disease, and in age-related diseases
such as Alzheimer's disease.
-
- When glucose, the most abundant sugar in the body, attaches
itself to proteins without the aid of enzymes, a series of chemical reactions
results in the formation and eventual accumulation of irreversible bonds,
or Crosslinks, between proteins. This "molecular glue", known
as Advanced Glycosylation End-product, or A.G.E.s, causes proteins that
are normally flexible and separate to become rigid and attached, making
cells, tissues and organs stiff and increasingly less functional. In healthy
individuals, this process occurs naturally, though slowly, as the body
ages. In diabetic patients, the rate of A.G.E accumulation and the extent
of protein cross-linking is accelerated, probably playing a role in many
medical disorders.
-
- The nonenzymatic reaction between glucose and proteins,
known as the Maillard or browning reaction, begins when sugar carbonyl
groups and protein amino groups combine, forming Schiff bases. These unstable
combinations quickly rearrange into somewhat more stable substances called
Amadori products. On long-lived proteins that are not normally recycled
within the body for months or years, problems can develop when some of
the Amadori products dehydrate. They then rearrange themselves forming
A.G.E.s and eventually mediate the cross-linking of proteins.
-
- In the early 1980s, researchers speculated that large
amounts of A.G.E.s occurred in diabetic patients as a result of their elevated
blood sugar levels. The A.G.E.s could be the missing link between diabetes
itself and the devastating complications of the disease which occur after
years of high blood sugar. Subsequent research conducted at more than 40
institutions around the world has supported this hypothesis, offering encouragement
that severe diabetic complications such as kidney failure, blindness, nerve
damage, hypertension, stroke, heart attack, skin ulcers and lower extremity
amputations can potentially be prevented or controlled. Currently there
are few viable alternatives for the prevention or treatment of diabetic
complications.
-
- The effect of diabetes on numerous organs and tissues
has been described as accelerated aging because of the similarity between
certain diabetic complications like cataract, joint stiffness and atherosclerosis
(a build-up of plaque in the artery walls) and disorders of the elderly.
Research suggests that if excess glucose hastens the onset of complications
in diabetic over a relatively short time-span, normal amounts of glucose
might play a part in a wide range of age-related disorders that occur much
more slowly and appear only later in life. For example, studies indicate
that nonenzymatic glycosylation of the eye's lens proteins may contribute
to the formation of cataracts. More recent studies implicate A.G.E.s in
age-related disorders such as Alzheimer's disease and stroke.
-
- Similarly, scientists speculate that glucose encourages
plaque formation characteristic of atherosclerosis by causing A.G.E.s to
develop on the collagen in blood vessel walls. Circulating low-density
lipoproteins or LDL are also subject to A.G.E. chemistry and may be trapped
from the blood and accumulate to form cholesterol deposits.
-
- Alteon's current research and drug development focused
on A.G.E. technology takes two directions: the prevention or slowing of
A.G.E. formation, and the breaking of A.G.E. Crosslinks between proteins
in order to prevent or reverse damage.
-
- SIGHTINGS HOMEPAGE
- This
Site Served by TheHostPros
|