Eric Bland, Discovery News |
Nov. 7, 2008 -- Eat more than you should. Stay skinny. Run twice as far. Those are the big claims coming from a new drug study from Sirtris Pharmaceuticals, Inc., based in Cambridge, Mass. This latest study clears the way for human clinical trials of SRT1720, often touted as an "anti-aging pill."
SRT1720 activates the same receptor as the much-discussed resveratrol, the chemical in red wine that may slow some effects of aging. Both resveratrol and SRT1720 are being tested as a way to treat type-two diabetes first, and possibly other age-related diseases, later.
"We are very excited by these results," said Michelle Dipp of Sirtris. "These compounds are mimicking calorie restriction and exercise while lowering levels of glucose and insulin in mice. It's a game changer."
The European scientists overfed two groups of mice by about 40 percent. For a person, that would be close to eating 3,000 calories a day, enough to pack on significant weight.
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The mice were first divided into a control group and test group. The test group was given two doses of SIRT1720: 100 mg or 500 mg.
After 15 weeks of eating the high-calorie diet, the control mice gained significant weight. The mice taking 500 mg of the drug, however, gained no weight. The cholesterol levels of the mice on the drug also improved.
The animals' exercise habits were also recorded. Mice without SRT1720 ran for roughly half a mile. Mice given 100 mg ran roughly seven-tenths of a mile. And mice on 500 mg of SRT1720 were able to run a full mile, twice the distance of untreated mice.
Dipp won't speculate on the drug's upper limits, other than to say that tests have shown that above 500 mg, its effects plateau. SRT1720 has no known side effects.
The research, led by Johan Auwerx at the Ecole Polytechnique Federale de Lausanne (EPFL) in Switzerland, was published this week in the journal Cell Metabolism.
The new study echoes results published earlier in Nature with resveratrol, the chemical in red wine that led to much discussion about the "French paradox," the seeming ability of French people to eat high-calorie meals, with a glass of red wine, and remain thin. (To get the levels in the study, a person would have to drink dozens of bottles a day.)
SRT1720 is about 1,000 times more powerful that resveratrol, say the researchers. The two chemicals are not related structurally, but both influence the same chemical pathway in the body -- in particular, a type of receptor called SIRT1.
SRT1720 is more powerful than resveratrol because the body doesn't break the drug apart as quickly as it does resveratrol, making it more efficient at binding to the receptors.
The SIRT1 receptor is also activated during caloric restriction diets, which have been shown to lengthen life span in multiple animal models, and during exercise.
SIRT1 receptors are found in mitochondria, often called the powerhouse of the cell because of all the energy they produce.
Cells start out with lots of mitochondria. As the body ages, the mitochondria start to die off or fail.
While more research is needed to prove the connections, mitochondria are suspected to contribute to age-related diseases such as cancer, diabetes and Alzheimer's. Sirtris hopes SRT1720 will eventually be approved to treat these age-related diseases as well.
SRT1720 would be used as a therapeutic drug, not a preventative measure. "The FDA doesn't have a clear approval path for disease prevention," said Dipp. "It does have paths for treating disease, however, and that's what we are going after."
Rafael de Cabo, a researcher at the National Institutes of Health who studies SRT1720's life-extending effects on mice but was not involved in the European study, says that the results are "fantastic and well done."
Still, he urges patience; mice are very different creatures than humans, and more research needs to be done before SRT1720 or its weaker counterpart, resveratrol, are taken by humans.
"I always get the same question [about resveratrol]; how much should I take?" said de Cabo. "I don't take it, and until we have more data, I don't think other people should take it either."
source: discovery.com
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