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January 4, 2011

Lifespan Drugs

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  National Institute on Aging

U.S. Administration on Aging

Aging With Dignity

Aging Research Center

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The search for the "fountain of youth" has led anti-aging researchers towards some drugs that are currently used for treating Type 2 diabetes. This ScienCentral News video has more.

Eat Better, Live Longer

With around 64 percent of the population is either overweight or obese, health issues relating to being overweight have become almost epidemic in the U.S.

Obesity causes "metabolic syndrome" — in which insulin-resistance leads to diabetes, heart disease and other aging diseases. Meanwhile, it's been observed that throughout the animal kingdom, animals from worms to mice to monkeys live longer, healthier lives when eating very low calorie diets. Anti-aging researchers say the evidence all shows that metabolic function is closely linked to the aging process.

"Just reducing intake of calories has so many positive effects and we'd like to find the switches," says geneticist Stephen Spindler, professor of biochemistry at the University of California at Riverside. "There must be relatively few switches that that throws to cause us to change from a rapid aging, higher-disease state to a slower aging lower-disease state."

As reported in Discover magazine, some biotech companies like Massachusetts-based Elixir Pharmaceuticals, want to design new drugs to mimic those effects. But Elixir researchers also predict that some already widely-used drugs may turn out to slow aging. "There are indeed medicines that are currently available that treat metabolic function that probably have a positive effect on lifespan," says Bill Heiden, Elixir President and CEO.

Now Spindler reports a study in mice that supports that idea. Spindler and his colleagues use DNA microarrays to hack into the messages coded in our DNA. "Your body's kind of like a big multinational corporation... It's got centers in different parts of the body that do different things. So your brain does something sort of like corporate headquarters… the manufacturing is going on somewhere else like in the liver, and your receiving is down in your intestines. All those parts of the body communicate with each other and they've got instructions, sets of instructions that tell them what to do," he explains. "And so it's like we're intercepting all of the emails and all of the instructions that all those different parts of the body are sending to each other."

The research team's earlier work had shown that just eight weeks on a calorie-restricted diet had reduced the size of tumors in mice. "We were a little surprised by that that calorie-restriction was able to reverse the effects of tumors, that already existed so quickly, in the body and so we wanted to try and find out what the signals are that are involved in that reversal," he says.

Spindler's research team fed some 20-month-old mice (about 50 or 60 in human years) a low-calorie diet, while others got a normal diet containing one of several drugs that affect insulin and metabolic function. After eight weeks, they compared the response to the treatments by analyzing liver samples to decode what genetic messages it sent and received.

The most common drug used in managing Type 2 diabetes, generically known as Metformin, was a standout — it sparked a very similar pattern to calorie-restriction."Metformin did a wonderful job of reproducing those effects," says pindler "It looks almost exactly like calorie restriction in its effects. And so we're hopeful that that one drug might have similar effects on lifespan and on health."

But they warn that it's not known how Metformin would affect healthy, non-diabetic people, and caution against taking it — reminding us that all drugs have the potential to cause negative side effects.

"Unfortunately we don't really know yet whether that will mean that metformin will extend the lifespan of healthy animals or healthy people," Spindler says. "I hope that healthy, nondiabetic people won't begin buying metformin and taking it. I think anytime you start experimenting on yourself that you're entering dangerous territory."

Elixir CEO Heiden agrees, saying only a long term clinical trial can actually confirm whether any anti-aging treatment will work for people. For now, Spindler says he hopes drug developers will be able to use this method to discover new treatments with the same benefits but fewer side effects than existing diabetes Drugs.

Meanwhile Spindler points out that losing weight if you are overweight, exercising and quitting smoking are known to increase your life expectancy.

Spindler's research was reported in Discover, October 2005 and published in the September, 2005 issue of Physiological Genomics, and was funded by the Life Extension Foundation.

       email to a friend by Lindsay Carswell

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