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Diet Aids May Promote Healthy Aging

Studies find they give old rats vigor, memory

MONDAY, Feb. 18, 2002 (HealthDayNews) -- The combination of two widely available diet supplements may reverse the effects of aging at its most basic cellular level, a trio of new studies show.

The supplements, a protein important in fuel burning and a potent antioxidant, aren't quite the Fountain of Youth. But they do give older rats more vim and vigor and improve their memory when added to their food and water, the researchers say.

"We don't know anything about the effects of these supplements on life span," says Tory Hagen, a biochemist at Oregon State University and a co-author of two of the papers. Rather, Hagen says, the combination "seems to maintain the 'health span' of these animals" by allowing them to age more gracefully. "And that is our great hope for translating this work in animals into human studies," Hagen adds.

Hagen's colleagues in California are now organizing a small study in a group of healthy elderly people to see how well they tolerate the supplement combo and if it improves their stamina. And an Alameda, Calif. company, Juvenon, Inc., is trying to commercialize the supplement regimen as an anti-aging therapy.

The three studies, which appear in the Feb. 19 issue of the Proceedings of the National Academy of Sciences, hinge on specialized parts of cells called mitochondria. These are the energy factories of tissue, converting chemical fuel, like fatty acids, into the molecule ATP. The breakdown of ATP powers everything from nerve signals to muscle movement.

As the body ages, mitochondria become less efficient. One reason is that they literally rust on the inside, as charged oxygen atoms that accumulate over time degrade the enzymes that help them do their job.

In theory, then, healing this damage might restore mitochondria to shades of their youthful agility.

The latest studies attempt this in two ways. The first involves delivering a protein, acetyl-L-carnitine (ALCAR), which overcomes age-related damage to a key mitochondrial enzyme called carnitine acetyltransferase. The second tack hits the problem from the oxidation angle, using lipoic acid (LA) to mop up the oxygen free radicals that plague the organelles. [Lipoic acid may also repair damaged mitochondrial enzymes another way, but this "one-two punch" hasn't been proved, Hagen says.]

In one study, Hagen, Bruce Ames, a biochemist at the University of California-Berkeley, and their colleagues gave ALCAR and LA (both together and separately) to young adult rats aged 2-4 months and to more august animals aged 24-28 months, roughly equivalent to the human 70s and 80s.

After up to a month on the combination diet, the lab was like the set of the movie "Cocoon." Older animals were scampering around their cages like they did as youngsters, and even the younger adults had more energy, Hagen says. Tests of the older animals' cells showed that their mitochondria were markedly more efficient after eating the supplement combination than if they didn't get the compounds. And other tests found that the two supplements appeared to reduce oxidative damage to their cells, too.

In the second trial, Hagen, Ames and their colleagues showed that memory loss in old rats was associated with the decay of mitochondria -- and that they could partly reverse this decline by feeding the animals high doses of ALCAR and LA together. Hagen says the old, treated rodents seemed to have the memory of young adults, "but this is pure supposition," he adds.

And in the third study, tests of the chemicals show that they reduce age-related damage to mitochondria in brain cells. LA may also help in the brain in another way, by reducing the oxidative stress from iron and copper molecules that build up in the organ.

The new work used fairly typical quantities of LA but enormous doses of ALCAR, which would translate into tens of grams a day for humans -- an amount Hagen says he "wouldn't recommend" to people.

"We can go much lower and still see the same things in animals, and that may translate into a useful supplement for human beings. But right now these doses are more in the pharmacological range rather than a supplement range," he adds.

Jeffrey Blumberg, a Tufts University antioxidant expert, says the work is "exciting," and that "it's nice to see such a good correlation between changes in performance and biological markers of oxidative stress."

But Blumberg cautions that the "prime-time part" will be when researchers demonstrate that the supplements have the same effects in humans as they do in rats. The scientists also need to show that the effect of the supplement therapy is more than a merely fleeting burst of energy at life's end.

The track record of antioxidant supplements for treating human disease has been disappointing. Vitamin E, for example, was long touted as being heart-protective, until studies in patients failed to find any such benefit from the nutrient.

Still, Blumberg says those trials have tended to include sick people taking a wide range of drugs for various conditions; they don't address whether an antioxidant could help reverse the effects of aging in a group of healthy subjects.

"Just because an antioxidant doesn't work in treating a patient with cancer or heart disease doesn't mean it won't work" to prevent age-related cell damage, he says.

What To Do

To learn more about antioxidants, visit the Canadian National Institute of Nutrition or the National Institutes of Health's Office of Dietary Supplements.

For a more skeptical view of antioxidants, check out Quackwatch.

SOURCES: Interviews with Tory M. Hagen, Ph.D., assistant professor of biochemistry and biophysics, Oregon State University, Corvalis; Jeffrey Blumberg, Ph.D., chief of antioxidants research laboratory, and senior scientist, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston; Feb. 19, 2002, Proceedings of the National Academy of Sciences
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