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Bucking Old Age

Research at Novato's Buck Institute may lead to anti-aging pill

By Joy Lanzendorfer

It sits on top of a hill like a Greek temple above Novato. The scientists who work there research anti-aging, an area of science that conjures images of regeneration chambers and magic serums. It's the only facility of its kind in the United States and only one of three of its kind in the world, yet few people understand exactly what the Buck Institute does.

Driving up the long hill to the Buck Institute, security gates and signs warn against trespassing. Buck invested in these measures not to protect secret experiments but as a response to skateboarders and other curiosity seekers who were drawn to the building's prime location. The mystique is enhanced by the main building, a half-rectangular, half-circular creation spliced by a giant triangle. I. M. Pei, the architect who designed the controversial pyramid in the Louvre, built the Buck Institute. It's no surprise people wonder about this place.

"There is definitely an impression with the public that the scientists are doing something up on the hill, something behind closed doors," says Buck Institute CEO Dale Bredesen, Md. "Shortly after Buck first formed, I was walking my dog in the park below and a woman pointed up to the institute and said to me, 'You know, they are torturing primates up there.'"

The Buck Institute was founded in 1999 by the Leonard and Beryl Buck Foundation, which accounts for about one-third of the institute's budget. The rest of the budget is primarily provided through grants. As an independent nonprofit, Buck is not involved in drug research or any other commercial development, though it has begun to license its research to biotech companies.

The institute's focus is on good old-fashioned scientific research. But no torturing of primates goes on. Mice, and much simpler creatures, like the microscopic nematode worm, are the preferred specimens for the Buck's three main areas of research: studying age-related diseases such as Alzheimer's and Parkinson's (last December a Buck study reported that a diseased brain may try to heal itself by growing new nerve cells, a possible breakthrough for treating Alzheimer's); investigating the aging process itself; and researching such technologies as genomics that support the first two areas.

In June, Buck will open a new lab under scientist Pankaj Kapahi, studying the effects of caloric restriction on the life span of fruit flies. Scientists have found that for many species, cutting calories of a diet to as little as two-thirds the normal intake while still maintaining essential nutrients tends to increase the creature's life span. The process is called "under-nutrition."

"The evidence shows that when keeping with good nutrition, restricting eating may lead to a longer life," says Bredesen. "Kapahi is actually weighing little fruit flies to see the effect of their diet."

For example, cutting 30 percent of calories from the diet of rats increased their life span by 30 percent. The same animals tested under caloric restriction also get age-related ailments like cardiovascular disease or cancer much later in life than is normal for that species.

The work of Gordon Lithgow, another Buck Institute scientist, examines aging in nematode worms. One aspect of his research shows the effect of oxidative stress on cells. Last year, Lithgow linked a stress-management protein found in a mutant strain of genes to longevity in worms. The worms that had this strain lived 70 percent longer than other worms.

Some scientists have linked caloric reduction and oxidative stress together, suggesting that caloric reduction leads to less oxidative stress, and thus longer life spans.

While there's obviously huge differences between worms and humans, Lithgow believes it's fair to consider the implications of his research for people.

"When I first got into this, I thought studying worms was an interesting biological problem, but not something you can apply to human beings," he says. "But it turns out it is connected. First of all, worms share many of our genes, so we are really more similar than anyone thought. Secondly, aging in a worm is remarkably similar to aging in people."

The application of these and other experiments may lead to an anti-aging drug. It may sound like science fiction, but scientists believe they are only 10 years away from a pill that would slow the aging process. A person who took this pill throughout his or her lifetime might look and act 40 at 60.

"The chances of it happening are very high," says Bredesen. "Look at just the genetic manipulations alone. We already have worms that are living six times as long--that's a 400-year-old worm. An anti-aging pill is extremely feasible."

Currently, of course, there is no single drug compound proven to lengthen the human lifespan, even though the average spam-filled e-mail box may seem to say otherwise. Every day, someone new seems to be offering a new magic cure to slow aging.

The proliferation of anti-aging pseudo-science has alarmed the scientists at Buck.

"It's completely understandable," says Lithgow. "You have the scientists on their white palace on the hill telling you one thing and all these voices of commerce telling you another. The confusion among people about anti-aging is almost palpable."

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From the June 2-8, 2004 issue of the North Bay Bohemian.

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