Unlocking the Secrets of Longevity

May 22, 2008 — -- Eating right, exercise and a positive attitude have long been the best ways to ensure longevity. Now, a series of scientific breakthroughs may help extend life even longer.

Up to recently, modern medicine's prescription for creaky, aging bodies has been to target each ailment in ways that can ease -- if not halt -- what seems like an inevitable decline.

Robert Butler, a physician and founding director of the National Institute on Aging, has called for a shift in how we address these problems.

"Instead of treating diseases one at a time, we should look more at the process of aging itself because we would get so much more mileage that way," said Butler.

Part of the groundwork for this type of approach began 15 years ago when the results of an intriguing lab study led many to rethink the fundamental understanding of how aging works.

It was around that time that a researcher at the University of California in San Francisco named Cynthia Kenyon had begun to tinker with the genes of Nematodes, tiny roundworms roughly the size of a comma.

Like any other creature, roundworms are made up of cells that, as they divide, accumulate damage over time. After a couple of weeks, the worms succumb to this buildup of wear and tear known as old age.

Kenyon, however, demonstrated that altering just one gene gave rise to worms that lived twice as long.

"What we saw with these long-lived mutants is that their cells don't have to just sit there and take it," said Kenyon. "Instead, special proteins are produced that strengthen the immune system, the body makes more antioxidants and its ability to repair DNA goes up."

Her study, published in Nature, has shown that aging is not fixed, but malleable. The discovery, taken some steps further, has tantalizing possibilities: If a similar gene exists in humans, a real-life fountain of youth may lie dormant within all of us. Researchers would just need to find it and figure out a way to turn it on.

"If you can slow down aging, your chances of not getting practically anything would go up. It's a new way of thinking," Kenyon said.

David Sinclair, a pathologist at Harvard University who has been on a quest to boost human life spans since boyhood, has identified what he believes are "anti-aging genes."

In 2004, Sinclair and his research team discovered that caloric restriction, a diet known to extend the life span of rats, activated a key gene called SIRT1. The researchers then fed a group of obese mice the chemical Resveratrol, a compound that had turned on similar genes in long-lived flies, fish and worms.

While the researchers saw a marked increase in life span, they also found that the mice staved off the consequences of consuming a high-fat diet. Their hearts and livers were healthier than other obese mice, and health complications linked to diabetes were nearly nonexistent.

"What's really encouraging though," Sinclair said, "is that they can run twice as far without ever have trained before. These are Lance Armstrong mice."

Sinclair suspects that Resveratrol, found in the skin of grapes and red wine, tricks the SIRT1 gene into producing enzymes that crank up the body defenses in the same manner as restricting calories -- without the hunger pangs of course.

Caloric restriction is "very difficult to do," said Sinclair. "Most people find it extremely unpleasant, if not impossible, to maintain. You also can't expect the elderly or the sick to go on these kinds of diets."

Unfortunately, achieving the same effect in humans with Resveratrol would require drinking hundreds of bottles of a wine a day, which is why Sinclair has founded a company to develop a molecule he hopes would be "1,000 times more potent" than Resveratrol.

As longevity researchers look to build on such promising findings, others in the scientific community are more cautious and warn that there may be some drawbacks to living to, say, 120.

David Meltzer, a medical economist at the University of Chicago, sees a possible scenario where people live longer, but have less enjoyable lives.

"One of the most obvious downsides," Meltzer said, "is that you also get extra years of life in retirement where you are consuming, but not earning, which means more money needs to be saved, rather than spent, in order to support yourself during those years."

"Living longer and living better aren't necessarily the same thing economically," he added.

Despite the potential benefits and pitfalls, the science of life extension is still very much in its infancy. Clinical studies, which have shown promise in animals, have yet to be duplicated in humans.

Also, tweaking the genetic circuitry that regulates aging may have limitations. Sinclair, who thinks a life-extending drug will come in the next decade, admits that he doesn't foresee a doubling or tripling of life span because the technology can't stretch it beyond a certain point.

"I would imagine people would be able to live about five to 10 years longer," said Sinclair.

"But I'd take an extra five quality years any day. Wouldn't you?"

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