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the long view

The most common treatment for type 2 diabetes – a generic drug called metformin – may do a lot more than just regulate insulin levels. Scientists studying its potential as an anti-aging pill say the drug slows the “burn rate” in living cells in ways that increase longevity.

Derived from a plant called French lilac, metformin costs pennies a pill. Studies in animals suggest the drug could delay the onset of chronic diseases, such as cancer and dementia, by “targeting the biology of aging,” said Dr. Nir Barzilai, director of aging research at Albert Einstein College of Medicine in New York. “You give it to nematodes [microscopic worms], you give it to rats, to mice – they all live longer.”

But worms and rodents are short-lived creatures. Could metformin have the same effect in humans?

Barzilai has teamed up with colleagues from more than a dozen research centres across North America to answer that question. They’re gearing up for a US$77-million clinical trial called TAME, short for “targeting aging with metformin,” and plan to start recruiting 3,000 adults aged 65 to 80 in the next year or so.

Barzilai predicts that people on the drug “will have less disease.” In observational studies, he pointed out, patients taking metformin for diabetes have shown lower rates of cancer, dementia and cardiovascular disease.

But observational studies of patients taking a drug for a specific disease are “very hard to interpret,” said Dr. Judy Wong, an associate professor of pharmaceutical sciences at the University of British Columbia. After all, one of the first things a physician tells a patient with type 2 diabetes is “you have to change your lifestyle,” said Wong, who studies how cellular changes and DNA damage contribute to aging. Patients often start exercising and watching what they eat in addition to taking metformin, so the drug alone may not account for the lower disease rates, she said.

Metformin is hardly the first compound hailed as an anti-aging wonder drug. The “red wine pill” (concentrated resveratrol) failed to live up to the hype after GlaxoSmithKline paid US$720-million in 2008 to acquire a biotech company touting its benefits. Meanwhile, rapamycin, a substance discovered in Easter Island soil, has prolonged life in dogs. But serious side-effects make this immune-suppressing drug an unlikely contender in the hunt for the pharmaceutical fountain of youth.

Metformin, by contrast, has both an enviable safety profile and a decades-long history of human use, said Dr. Michael Pollak, director of cancer prevention in the department of oncology at McGill University.

Metformin shows effects on energy production at the cellular level that may extend life, said Pollak, who has collaborated with Barzilai on studies of metformin. Cells generate energy using oxygen to burn glucose from the foods we eat. “Each cell is a bit like a furnace,” he said. Metformin reduces oxygen consumption to a “slow burn,” dialing down the pace of cell division, and with it, the aging process itself.

That’s if you believe the “rate of living” hypothesis, a controversial model of aging first proposed in the 1920s. Signs of aging, such as wrinkles and forgetfulness, do not appear after a set number of calendar years, said Pollak. Rather, they “occur after a certain number of cell divisions from the time you’re just a fertilized egg.”

Metformin may indeed affect energy production in cells, Wong said. “But there are other things that might be contributing to cellular aging as well.” If scientists manage to come up with a “magic potion” to fight aging, she said, “it will likely be a combination of drugs.”

Barzilai is so confident in metformin that he has lobbied the U.S. Food and Drug Administration to add wording such as “retards aging” on the packaging, provided he can prove the drug does for humans what it does for mice. Without this FDA indication, he said, insurers would refuse to cover metformin for patients who do not have diabetes.

The goal, he explained, is to prevent a whole cluster of diseases that grow common with age, including cancer, dementia and cardiovascular disease. “Any drug that will do this is basically targeting aging.”

But Pollak, the only Canadian researcher involved in the metformin trial, remains circumspect about the drug’s potential. Even if the TAME study ends up proving that metformin prevents age-related diseases, the drug’s effects might pale in comparison to the benefits of regular exercise and a healthy diet, he said. “I believe that [metformin] is not likely to be an antidote to a bad lifestyle.”

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