(4 of 9)
In recent years, some nutritionists have advocated diets high in fruits and vegetables containing carotenoids--substances that act as antioxidants by sopping up free radicals and carrying them out of the body. But antioxidants have an uneven record. In some studies they seem to be associated with a dramatic reduction in cancer or other diseases; in others, some antioxidants, such as beta-carotene, actually seem to be associated with an increase. In either event, few contemporary aging researchers think self-medicating at a salad bar is the best way to extend the human life-span. Far more promising might be new research into another by-product of cellular metabolism: glycosylation--or what cooks call browning.
When foods like turkey, bread and caramel are heated, proteins bind with sugars, causing the surface to darken and, in some cases, turn soft and sticky. In the 1970s, biochemists hypothesized that the same reaction might occur in the bodies of people suffering from diabetes, as excess glucose combined with proteins in the course of metabolism. When sugars and proteins bond, they attract other proteins, which form a sticky, weblike network that could stiffen joints, block arteries and cloud clear tissues like the lens of the eye, leading to cataracts. Since diabetics suffer from all these ailments, the biochemists guessed they were right.
But joint pain, circulatory disease and poor vision sound an awful lot like the symptoms of aging. Was it possible that as the cells of nondiabetics metabolize sugars, the same glycosylation process might take place, only much slower?
The idea that the grand tragedy of aging and dying might be nothing more than a body-wide process of caramelization was humbling, but more research provided still more proof. Studies of the collagen sac between the brain and skull in diabetics and the elderly turned up brown pigment characteristic of advanced glycosylation. "The glycosylation process is like the free-radical process," says Dr. Robert Butler, head of the International Longevity Center at Mount Sinai Medical Center in New York City. "It's a natural phenomenon that keeps us alive but also helps lead to aging."
In the years since the caramel theory was first advanced, the gooey glycosylation residue has been given an appropriate acronym: AGES, for advanced glycosylation end products. If residue from AGES do indeed gum up the body's works, however, there may now be a way to get things unstuck. Investigators at the Picower Institute for Medical Research in New York are working on a drug that acts as an AGES solvent. Known as pimagedine, the medication dissolves the connections between the AGES protein and the proteins that cluster around it. In one study, 18 patients taking pimagedine showed reduced blood levels of lipoproteins, the substances that act as precursors of artery-clogging cholesterol. In another, rats taking pimagedine did not exhibit any signs of heart disease.
"We're at the early stages of development, but we have a theory and proof of concept," says Dr. Richard Bucala, a Picower researcher. "The biochemistry of glycosylation occurs in a lot of medical conditions, so it's not a great leap to aging."