Q & A: AGEs and Aging; A Definite Link That Is Worth Breaking


Q & A: AGEs And Aging; A Definite Link That Is Worth Breaking

Blood by-products resulting from glycation are connected with diabetes, heart problems and aging. Studies show however, that the use of aminoguanidine may provide the best protection against these ills.

Q. In reading about aging, I've come across the term "glycation" on several occasions. What does this term mean? How does it relate to aging?

A. Glycation (also called glycosylation) involves the interaction of blood sugar (glucose) with protein molecules in the blood and tissues, which results in by-products called "advanced glycation endproducts" (AGEs). AGEs have been linked to pathologic damage in diabetes, cardiovascular disease and aging. The glycation theory of aging postulates that the production of AGEs is a fundamental aging process, and that any agent that reduces the activity of AGEs should slow aging and protect against diabetes and cardiovascular disease.

Evidence for the glycation theory of aging comes from a food restriction study in rats conducted by Ed Masoro and colleagues (J Geront, 44[1] pB20-2, Jan 1989) at the University of Texas Health Science Center in San Antonio. In this study, food restriction, which markedly retards aging in rats, was shown to produce significantly lower glucose and glycation levels in the experimental rats than in normally fed rats. Although this finding is consistent with the glycation theory of aging, food restriction also produces other changes, such as reduced oxidative stress, which support other theories of aging. It is still unclear whether elevated glycation is a cause or a consequence of aging.

The most investigated anti-glycation agent to date is aminoguanidine. In a recent study (Proc Natl Acad Sci, 93[9] p3902-7, Apr. 30, 1996), scientists at the Picower Institute for Medical Research in Manhasset, N.Y., looked at the effects of aminoguanidine on aging-related renal and vascular changes, as well as its effects on the accumulation of AGEs in non-diabetic female and Fischer Sprague-Dawley 344 rats.

They gave the experimental rats 0.1 percent aminoguanidine in their drinking water for 18 months. The results were the prevention of elevated AGEs (compared to controls), the prevention of age-linked vasodilatory impairment in response to acetylcholine and nitroglycerine, and the inhibition of age-related albuminuria and proteinuria.

"These data suggest," concluded the scientists, "that early interference with AGEs accumulation by treatment with aminoguanidine may impart significant protection against the progressive cardiovascular and renal decline afflicting the last decades of life."

Because of these and other results, the Life Extension Foundation has included aminoguanidine in our Lifespan Project to determine its effect on mean and maximum lifespan. Aminoguanidine is only available from the Alzheimer's Buyers Club in Switzerland, but two other anti-glycation agents -- alpha lipoic acid (also being studied in The Lifespan Project) and chromium -- can be obtained through the Foundation as dietary supplements.

Q. What causes the greatest production of damaging free radical activity in the body?

A. Free radicals are natural and useful by-products of vital life processes, such as energy production and immune function. It is only when free radical activity becomes excessive that damage occurs to the cells and tissues of the body. The body produces abundant supplies of antioxidant enzymes, such as superoxide dismutase, glutathione peroxidase and catalase, to prevent the damaging effects of excessive free radical activity.

The heaviest levels of free radical activity occur as a result of energy production in cellular power plants called mitochondria. Oxidative radicals generated by mitochondria appear to be the major source of the oxidative lesions that accumulate with age in the brain, heart, liver and other tissues in the body.

According to Bruce Ames and associates at the University of California at Berkeley, the contributing factors to age-related mitochondrial dysfunction include "proton leakage across the inner mitochondrial membrane, decreased membrane fluidity, and decreased levels and function of cardiolipin, which supports the function of many of the proteins of the inner mitochondrial membrane." (Proc Natl Acad Sci, 91[23]p10771-8, Nov. 8, 1994)

The body has two potent antioxidants -- alpha lipoic acid and coenzyme Q10 -- whose function (in part) is to inhibit free radical activity generated by mitochondria. Dietary supplementation with these two antioxidants is helpful in curbing the overflow of free radicals in the heart, brain and other tissues. Another agent which has been shown to reverse age-associated deficits in cellular function is acetyl-L-carnitine, a high-energy mitochondrial substrate that also is available as a dietary supplement.

Q. What is lycopene? What does it do? What foods contain lycopene?

A. Lycopene is a carotenoid, similar to beta-carotene. Carotenoids are nutrient compounds found in many fruits and vegetables. They are present in the blood and virtually all cells of the body. The major dietary sources of lycopene are tomatoes and tomato products. Lycopene is available as a dietary supplement.

Recent studies indicate that lycopene is the most important carotenoid for health and longevity (Arch Biochem Biophys, 336(1)pl-9, Dec. 1, 1996). Among the biological activities of lycopene are antioxidant action (singlet oxygen quenching and peroxyl radical scavenging), the induction of communication among cells, and growth control.

Research shows that lycopene may protect against various types of cancer, including prostate cancer. Laboratory studies have shown that lycopene can block the growth of cancer cells. Lycopene has been included in the Foundation's Lifespan Project to determine if it can extend lifespan in laboratory mice.

A. I read your article on homocysteine as a risk factor for heart attack and stroke ["Homocysteine And Heart Attacks, "July 1997] with great interest. Can you tell me whether there is any link between coffee drinking and homocysteine levels? I've heard that some studies show a correlation between coffee intake and the risk of heart disease, while others do not. I drink quite a bit of coffee and would like to know if this poses any risk to my health?

A. A recent study from Norway was the first to show a clear-cut correlation between coffee drinking and homocysteine levels. Ottar Nygard and colleagues at the University of Bergen looked at the relationship between various lifestyle factors and homocysteine levels in 16,000 men and women, 40 to 67 years of age. Their findings were reported in the January issue of the American Journal of Clinical Nutrition.

The Norwegian team found that, as average coffee consumption increased, so did homocysteine in the blood. This link was shown to be independent of the effects of diet, smoking, exercise or vitamin supplementation. Only people who drank decaffeinated coffee showed no link with homocysteine, and no homocysteine link was found with tea drinking.

There was no elevation of homocysteine associated with low coffee intake (one to three cups a day). It was only after the regular consumption of five or more cups of coffee a day that the link to homocysteine became apparent, with the higher the coffee intake the greater the elevation of homocysteine.

Most studies showing that coffee drinking increases the risk of heart attack have come from outside the United States. Since coffee drinking raises homocysteine levels, it may be that the difficulty in showing harm from coffee drinking in the U.S. may be because Americans have a significantly greater intake of folate and B vitamins, which help to reduce levels of homocysteine in the body.

If you wish to continue drinking coffee but wish to mitigate its risk to your health, you should eat more fresh fruits and vegetables and take vitamin supplements that include extra amounts of vitamin B6, vitamin B12, folic acid and trimethylglycine to help lower your homocysteine levels.

Q. I know cigarette smoking raises the risk of heart disease and lung cancer, but I've also heard that it accelerates aging. Is that true?

A. Yes. Heavy cigarette smokers show the signs of aging earlier and more intensely than nonsmokers. Among the aging effects of smoking are increased skin wrinkling -- especially on the face -- and a greater incidence of hair graying and baldness.

J.G. Mosley of the Leigh Infirmary in Lancashire, England, studied 606 subjects (268 men and 338 women), of whom 304 were smokers. After controlling for age, he found that smokers were four times more likely to have gray hair than nonsmokers. He also found a link between smoking and scalp hair loss.

If you're a smoker, you should make every effort to quit. If you continue to smoke, however, it is imperative that you take high doses of antioxidant vitamins such as beta-carotene, vitamin A, lycopene, vitamin C and vitamin E, as well as high doses of B complex vitamins, folic acid and trimethylglycine to reduce potentially toxic homocysteine levels, which are elevated in smokers.

Q. My father just underwent cancer chemotherapy. He's quite weak and his doctors have told him to get plenty of bed rest until he regains his strength. I'm wondering whether he might recover faster if he exercised. Is there any evidence regarding the risks and benefits of exercise in cancer chemotherapy patients?

A. Although exercise traditionally hasn't been part of rehabilitation after cancer chemotherapy, new research findings suggest that it may be beneficial. Recently, Fernando C. Dimeo of the Freiburg University Medical Center in Germany conducted a trial in which half of 32 patients participated in an exercise program after chemotherapy, while the other half served as controls. The results were reported in the May 1, 1997, issue of the journal Cancer.

The results showed that those in the exercise group were stronger, had more stamina, and had significantly higher concentrations of hemoglobin in their blood, indicating that their oxygen-carrying capacity had risen. They were able to resume their normal activities faster and reported feeling better sooner than the controls. The study was not carded on long enough to determine whether the patients undergoing exercise had a better outcome with regard to their cancer than the controls.

However, another recent study showed that exercise can help prevent cancer. In this study, which was reported in the May 1 issue of the New England Journal of Medicine, Inger Thune and her colleagues at the University of Tromso in Norway looked at 20,624 women. They found that women who regularly exercised cut their risk of breast cancer by 72 percent.

Life Extension Foundation.

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