An inexpensive diabetes drug slows the aging process in male monkeys and is particularly effective at the effects of aging on the brain to delay, as shown by a small study that tracked the animals for more than three years 1. The results raise the possibility that the widely used drug, Metformin, could one day be used to delay aging in humans.

The monkeys that received metformin daily showed slower recovery age-related brain regression than those who did not receive the drug. In addition, their neuronal activity was similar to that of monkeys about six years younger (equivalent to about 18 human years), and the animals had improved cognition and preserved liver functions.

This on September 12th inCellpublished study suggests that although death is inevitable, "aging as we know it does not have to be that way," says Nir Barzilai, a geroscientist at the Albert Einstein College of Medicine in New York City who was not involved in the study.

A medicine in the medicine cabinet

Metformin has been used to lower blood sugar levels in people for more than 60 years Type 2 diabetes and is the second most prescribed drug in the United States. The drug has long been known to to have effects beyond the treatment of diabetes, which has led researchers to also study it against conditions such as cancer, cardiovascular disease and aging.

Data from worms, rodents, flies and humans who took the drug to treat diabetes suggest that the drug may have anti-aging effects. But its anti-aging effectiveness has not been tested directly in primates, and it is unclear whether its potential anti-aging effects are achieved through lowering blood sugar or through a separate mechanism.

This led Guanghui Liu, a biologist who studies aging at the Chinese Academy of Sciences in Beijing, and his colleagues to test the drug on 12 older male goat eumacia (Macaca fascicularis) to test; another 16 older monkeys and 18 young or middle-aged animals served as controls. The treated monkeys received the standard dose of metformin daily, which is also used to control diabetes in humans. The animals took the drug for 40 months, which is about 13 years for humans.

During the study, Liu and his colleagues collected samples from 79 types of tissue and organs from the monkeys, imaged the animals' brains and conducted routine physical examinations. By analyzing the cellular activity in the samples, the researchers were able to create a computer-based model to to determine the “biological age” of the tissues, which may be behind or above the animals' age in years since birth.

Slow down the clock

The researchers found that the drug slowed the biological aging of many tissues, including the lungs, kidneys, liver, skin and the frontal cortex of the brain. They also discovered that it Reduced chronic inflammation, an important feature of aging. The study wasn't designed to find out whether the drug extended the animals' lifespan; previous research has found no effect on lifespan 2, however, has been shown to extend healthy lifespan 3— the number of years an organism lives healthy.

This means that metformin “can effectively reverse organ aging in monkeys,” Liu says. The authors also identified a potential way the drug protects the brain: It activates a protein called NRF2, which protects against cell damage triggered by injury and inflammation.

This study is the "most quantitative and thorough examination of metformin's effects beyond mice that I have seen," says Alex Soukas, a molecular geneticist at Massachusetts General Hospital in Boston. “It was a surprise to see how broad the drug’s effects were across different tissue types.”

Inexpensive drug, expensive study

Although these results are encouraging, further research will be needed to study the drug before it can be validated as an anti-aging compound in humans, says Liu.

For one thing, only 12 monkeys received the drug. Soukas would therefore like to see a repeat of this study or one that includes more animals. Additionally, the researchers only tested male animals, which Rafael de Cabo, a translational geroscientist at the National Institute on Aging in Baltimore, Maryland, considers concerning. He acknowledges that it is extremely expensive to conduct these types of long-term experiments, but adds that it is important to understand aging in females as well there are often large differences between the genders.

Meanwhile, Liu and his colleagues a study with 120 people launched in collaboration with biopharmaceutical company Merck in Darmstadt, Germany, which develops and produces metformin, to test whether the drug delays aging in humans.

Barzilai has even bigger ambitions: He and his colleagues have sought to raise $50 million to study the drug in a study of 3,000 people ages 65 to 79 over 6 years. Research into metformin and other anti-aging candidates could one day mean that doctors can focus more on keeping people healthy for as long as possible rather than treating disease, he says.