Is the sand of time sugar? Some top researchers believe that this natural sweetener may not only speed up but even cause, aging.
Poor sugar, It’s been blamed for almost everything from excess poundage to diabetes. To that long list, we might now have to add one more cause for concern. A sudden rush of sugar in the bloodstream may speed up the aging process.
The earliest suspicions surfaced about 15 years ago when work on sugar aging link begins in a medical biochemistry lab at Rockefeller University in New York City, where Anthony Cerami, Ph, D., and his colleagues are still pursuing sugar’s role in the aging process.
It was Cerami who first noticed that the same chemical process that makes a streak toughen and turn down during cooling – a spontaneous reaction between sugar and protein called the “browning reaction” – occurs in human cells, particularly as they age. Indeed, approval to market a drug designed to halt this reaction is perhaps two to three years away. In time, it may help solve many age-related problems, from wrinkles to cataracts to certain types of cancer.
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According to Cerami, sugar is one of the culprits that set the again process in motion. Glucose is the basic energy source for human beings, the substance in which our cells are constantly bathed throughout our lifetime. Most of the food we eat is broken down into glucose and sugars. To understand how glucose might help trigger the problem of aging Cerami looked at how an excessive amount of this sugar behaves in diabetes because diabetics tend to suffer age-related complications – such as atherosclerosis, cataracts, and joint stiffness – much earlier than most people.
When glucose enters the bloodstream from the intestine, the same is taken up by cells and used as fuel; the rest is stored as glycogen in the liver and the muscles or is converted to fat and stored in fat cells until the body needs it. Under normal circumstances, the level of glucose in the blood kept remarkably stable by the hormone insulin. Diabetes results from a shortage of (or inability to use) insulin, which allows too much glucose to build up in the bloodstream, left unchecked, this would be a death sentence, but of course, it can be treated that insulin therapy and a carefully controlled diet. Even with such treatment, however, problems of aging occur earlier.
Cerami and then colleague Ronald J. Koenig found that protein molecules, which make up part of the structure of all cells, can be deeply affected by the elevated glucose level in diabetics’ blood. Over a period of a week to months, a small number of glucose molecules combine with some of the protein molecules to form “advanced glycosylation end products,” or ages. (This, in fact, is the browning reaction.) The AGE particles in turn act like glue, sticking some of the other protein molecules together in a rigid latticework pattern called cross-linking. When protein clumps together in this way, they can clog arteries; blur vision, damage kidneys, and lungs – conditions often associated with aging. It occurred to Cerami that glucose might have destructive potential in the bodies of nondiabetics, too. Since glucose affected proteins play a role in the age-related diseases for which the diabetic is at risk early in life, they might play a role in the same disease when they happen later.
Sugar’s Stiffening Effect
Cerami began examining nondiabetics’ longer-lived proteins for evidence of the process. Among such proteins are those making up the lens of the eye. When Cerami soaked these crystalline proteins in a glucose solution, the mixture turned opaque (resembling a lens with a cataract) and the proteins clumped together. It was the browning reaction all over again, and it led Cerami to believe that cataracts are formed with the help of glucose.
Preliminary research of several centers in the United States and Britain appears to confirm the connection between sugar and contracts, and aging skin.
Epidemiologist Paul F. Jacques, at the USDA’s Human Nutrition Research Centre on Again in Boston, has shown in preliminary studies that galactose, derived from the sugar in milk, may play a role in the development of cataracts, By itself, galactose is destructive to the lens of the eye, but it’s normally metabolized quickly by the enzyme. In people who are deficient in this enzyme, Jacques found, this conversion process is slowed, eventually causing cataracts.
Further sugar aging links come from Cerami’s research on collagen. Collagen is the most abundant protein in the human body. It is found in the skin and in all the connective tissues, and it serves to “glue” cells together. As collagen grows old, it becomes stiff – as we do. Cerami began, incubating the tendon fibers of young rats in various sugar solutions to see whether glucose could cause cross-linking in collagen. It did and the tendon fibers stiffened and broke more easily when stretched. Because of the glucose, the tendon fibers of young rats became more like those of older rats. Once again, the glucose protein reaction had speed up the aging process.
Cerami’s results were reinforced by those of Vincent M. Monnier, associate professor of pathology at Case Western Reserve University in Cleveland. Monnier found that centenarians have as much as ten times more sugar-laden, children suggesting that sugar does indeed play a key role in aging.
Other possible aging connection: Cerami thinks glucose hardened collagen may trap cholesterol on the walls of blood vases, causing atherosclerosis, or hardening of the arteries. And he and lab co-worker Richard Bucala, have recently begun to explore the possibility that glucose, reacting with DNA cause genetic mutations that can lead to cancer.
“I became intrigued by the whole question of increased incidence of cancer with age,” Cerami says. It was plausible that AGEs might accumulate on DNA, leading to alteration of genetic material. Thus, damaged cells might be unable to repair themselves or properly reproduce. The immune system could also be affected by glucose-induced mutations undermining its ability to keep cancerous cells in check. Cerami and other researchers have discovered that AGEs can indeed cause mutations in bacterial DNA. Next on the research agenda is studying mammalian cells in culture to see whether the same sorts of changes in genetic material occur.
Control Sugar, Control Aging
What can be done to prevent the destruction wrought by the browning reaction in the body? One tentative suggestion is to limit dietary intake of sugar. (Nutritionally, this is no problem). But since almost all food is ultimately converted by the body into sugar, can this really be effective? The research is hardly conclusive; still, some scientists say, maybe.
British researchers Anna Furth, a biologist at Open University, and John Harding, of the department of ophthalmology at Oxford University, suggest that heavy sugar snaking can adversely affect even non-diabetic people. When we take in a candy bar’s worth of sugar, the level of glucose in the blood rises sharply, and as insulin struggles to cope with it. A sudden rush of glucose in the bloodstream (whether from that candy bar or a glass or orange juice – remember, fruits contain fructose, which is, of course, sugar!) begins the browning reaction that causes the protein to cross-link.
On the basis of preliminary studies, the researchers think aspirin and ibuprofen may help protect protein molecules from marauding glucose – though it’s clearly too soon to translate that theory into action. Perhaps one of the most effective ways to protect you, they say, is to take carbohydrates as part of a mixed meal with protein, fat, and fiber and no crab snacking on an early stomach.
Taking another tack, researchers theorize that there should be a way to remove the end products of the browning reactions, AGEs before they’re able to glue protein in a cross-link. One solution may be to supplement macrophages, immune system scavengers that remove cellular debris, including AGEs. Cerami observes that macrophages are thought to become less efficient as people grow older and that AGEs may build up in places not easily reached for cleanup. A drug to improve the macrophage removal system is one long term hope.
An even better bet is a drug to prevent the formation of AGEs in the first place. Cerami and two former Rockefeller colleagues, Micheal Brownlee and Peter Ulrich, have already produced such a drug, called aminoguanidine. Trials with diabetic rats have shown that it can greatly inhibit the formation of AGEs. Aminoguanidine is currently being tested on human diabetics. Elsewhere, trials are under way using a skin cream version that could retard the effects of aging. If the results lead to FDA approval, marketing of the products would be two to three years away.
The possibilities are exciting, but Cerami has little interest in making people live forever. Instead, he’s focused on preventing the complications of growing old. “It’s getting up in the morning and facing a lot of physical problems” that makes aging unpleasant, he says. “Our research is not aimed at letting people live to be 400, but at improving the quality o life.”
Avoiding the Sugar Rush
Are some foods more likely to end up as glucose than others? Or the six essential nutrient groups the body needs, water, vitamins, minerals do not convert to glucose at all. But according to Gail C. Frank, professor of nutrition at California State University in Long Beach and a spokesperson for the American Dietetic Association, 100 percent of all carbohydrates (sugar and starches) do wind up as glucose in the blood, along with 59 percent of proteins and 10 percent of fats. Thus in a sense, it doesn’t whether you ingest table sugar (sucrose), fruit sugar (fructose) or starches such as those in potato or pasta, they’re converted to glucose eventually.
But Frank suggests that if you’re seeking to avoid that “sudden rush of glucose” that research Furth and Harding believe may exacerbate the protein cross-linking involved in aging, a solid food, such as a banana, will be absorbed into the bloodstream much more slowly then a liquid, such as a glass of orange juice. Moreover, she notes that sugars eaten by them (e.g. hard candies) are absorbed more quickly than starches taken alone, since the chemical structure of starch is much more complex.
Your best anti aging bet may be to make a habit of consuming sugars and starches as part of a full meal that also includes protein, fat and especially fiber. A glass of orange juice on an empty stomach becomes glucose in the blood stream in as little as a minute; while nutrient balanced meal takes several hours to digest, there by prolonging the absorption of glucose.