A.G.E. Formation The Road to Diabetes, Disease and Aging

greenspun.com : LUSENET : TB2K spinoff uncensored : One Thread

A.G.E. Formation - The Road To Diabetes, Disease, & Aging

http://www.alteonpharma.com/age_backgrounder.htm 3-14-00 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.

-- suzy (suzy@nowhere.com), March 15, 2000


Thanks for the post, Suzy

-- Very (Grateful@still.here), March 15, 2000.

I wonder how you prevent this condition. I know on the web there is an interesting document--Multidisciplinary Approach to Diabetic Neuropathy, which emphasizes GLAs--a certain kind of fat found in such substances as evening primrose oil... If you read this, you'll see that it relates to the oxygenation of the blood... Sorry I can't give you a link.

-- Mara (MaraWayne@aol.com), March 15, 2000.

Hi Mara, I have wondered too, if there would be some simple and over looked way to stop or reverse this process. Find the possibilities interesting too.

-- suzy (suzy@nowhere.com), March 15, 2000.

Moderation questions? read the FAQ