Rat Study Suggests Supplements Can Extend Life

Tory Hagen is amazed every time he looks at the old rats in his laboratory at the Linus Pauling Institute on the campus of Oregon State University in Corvallis. They don't act like old rats. They think they're still young.

For several years now Hagen and his illustrious colleague, biochemist Bruce Ames of the University of California, Berkeley, have been feeding their old rats a mixture of two common nutritional supplements to see if they could turn back the paws of time. Working on the theory that aging is caused at least partly by dysfunction within the cellular structure itself, they think what works for rats may also work for humans.

If they are right, it should be possible to reduce the many disheartening effects of aging by simply popping a pill. But like so many so-called breakthroughs in the ageless search for an end to aging, there's no proof that Hagen and Ames are right. But that could soon change.

A new program under the auspices of the National Institutes of Health is designed to evaluate alternative forms of medicine, like the efficacy of dietary supplements, and it has established the first two "Centers of Excellence for Research." One will study acupuncture. The other will look at the old rats, and the claims that have been made in their behalf.

The second award totals $5.8 million, enough to begin clinical trials with humans, and the center is located on the Oregon State campus, conveniently near Hagen's old rats.

Works on Rats...

Hagen is pretty optimistic that it will work for humans, but he says he isn't sure.

"Humans aren't rats," he says.

But there's no confusion about the effect on rats.

"I'm rather flabbergasted by what we've seen," he says.

A dose of lipoic acid, a naturally occurring antioxidant found in green leafy vegetables, and carnitine, found in red meat, was all it took to make old rats act young again, or at least middle aged.

Not only were they far more energetic. It also became easier for them to learn, and their short term memory improved dramatically, much to the surprise of Hagen.

"I have to say that wasn't something I was expecting," he says.

Young rats were able to figure out how to escape from a damp dungeon called a "Morris water maze" literally within seconds, and they remembered how to do it the next time they found themselves plopped back in the maze. Initially, the old rats couldn't figure it out at all.

But when given the nutrients, they not only figured out how to get out of the maze, they remembered it as well.

Which, of course, brings us to the fundamental question of why.

Replacing Critical Substances

For half a century now scientists have known that a severely reduced intake of calories increases human life span dramatically, but it's still not clear why. But it does indicate that nutrients play a key role in the aging process. That's one of the reasons Hagen and Ames zeroed in on area of the cell that is critical to the processing of nutrients, or fuel, and that's the mitochondria.

"That's the power plant for the cell," Hagen says. It takes in raw materials, mainly carbohydrates, and converts them to energy so the cell can carry out its chores.

So it's critical to the cells survival, but it doesn't always get it right. Occasionally, the mitochondria turns some of the fuel it receives into dreaded free radicals, oxidants that attack the DNA in our bodies.

"The oxidants are very similar to what one sees in a nuclear explosion, or a nuclear reaction," says Hagen, an associate professor of biochemistry and biophysics at Oregon State. "So we are constantly irradiating ourselves via the mitochondria throughout our lives."

The production of free radicals increases as we age, leading Ames and Hagen to speculate that the mitochondria plays a key role in aging. So they began experimenting with two substances used by the mitochondria, lipoic acid and carnitine. Lipoic acid is used to convert fuel to energy, and carnitine is the "glue" that attaches to the fuel and hauls it into the power plant.

"To make a long story short, we found that carnitine levels decline precipitously with age," Hagen says. "We don't make enough of it as we get older."

So the researchers began giving supplements to rats in hopes of increasing the performance of the mitochondria.

"We're trying to see where we can tune up, or maintain a level that should be there but isn't," Hagen says.

What they found is now history. The rats performed like troopers, but will the same nutrients do the same for humans? Are they safe? These nutrients function as drugs, though not yet approved by the FDA for that purpose, and all drugs have some side effects. Lipoic acid, for example, is also an insulin regulator, so diabetics should not experiment with it.

Living Proof

The researchers haven't found the fountain of youth. According to the National Institute on Aging, one of several sponsors of the research, aging is a very complex process that is still poorly understood. There are at least 300 theories about why and how we age, and there is a general consensus that we will not see a significant increase in human life span for decades, or centuries, if at all.

That doesn't trouble Hagen because that's not really what he and Ames are looking for. They want to help us remain as healthy and as young as possible, right up until the end.

That goal fits nicely with the vision of the man whose name hangs over the door of the institute where Hagen now works. Two-time Nobel prize-winner Linus Pauling predicted decades ago that free radicals, or other oxidants, were causing many of our problems, including age-related declines. That's why he vociferously pushed for vitamin C, a natural antioxidant.

But like most of us, he hated the thought of getting old. I know that because a number of years ago I celebrated his 90th birthday with him. I followed him around for three days, from his fabulous estate on California's Big Sur coastline to Stanford University, where he taught a graduate seminar on chemistry.

While delivering his lecture, Pauling forgot something he was about to say. That happens to all of us from time to time, but the grand old man of science looked terrified as he stood speechless in front of his young audience. They probably figured he was getting senile.

Pulling himself together, he finally said, "I guess you're all wondering what we're doing over at the institute."

He picked up a piece of chalk and wrote a formula on one of three huge blackboards that blanketed three walls in the lecture hall. For nearly an hour, he expanded on the formula until it filled all three walls. Then he turned to the students, who sat with their mouths hanging open in absolute awe.

"Any questions?" he asked.

Not a one.

Now there's a man who knew how to stay young.
