Metformin is the main drug used to treat type 2 diabetes, but a new study in monkeys suggests it may one day be used to slow the aging of the brain.
Clues to the drug’s antiaging effects have previously been seen in retrospective studies of people taking this drug for diabetes and also in studies on worms, flies and rodents.
of metformin had not yet been tested in primates, so biologist Yuanhan Yang and his colleagues at the Chinese Academy of Sciences spent 40 months studying the effects of metformin on crab-eating macaques (Macaca fascicularis), one of our closest relatives.
The monkeys that participated in this experiment were all males between the ages of 13 and 16, the equivalent of 40-50 years of human development.
Some of the macaques received a daily dose of metformin for just over three years without interruption, which is roughly equivalent to standard treatment for people managing their type 2 diabetes, he writes.
The antiaging effects of metformin had not yet been tested in primates
Others of the same age received similar treatments that did not contain any drugs. Control groups of six young (3–5 years) and three middle-aged (10–12 years) male monkeys were also followed to specifically account for age effects.
“These findings suggest the potential of metformin in and possibly in the treatment of neurodegenerative and other chronic conditions,” the researchers write.
They assessed aging monkeys in terms of physiology, memory, learning and cognitive flexibility, as well as brain morphology.
The drug reduced fluctuations in gene transcription associated with aging in several different tissues, affecting pathways associated with aging, such as cell death and fibrosis, and reactivating aging-repressed pathways involved in development, such as DNA repair and lipid metabolism .
It reduced the biological age of old monkeys by several measures, slowed liver aging and improved chemical production. But most importantly, the study found that metformin did indeed delay brain aging and provide neuroprotection to the elderly monkeys, “saving” their frontal lobes by an average of nearly six years.
Similar effects in humans
They note that the study did not assess mortality or look at long-term effects after the macaques stopped receiving the drug.
Experts in the United States were impressed by the rigor of this experiment, which molecular geneticist Alex Soukas of Massachusetts General Hospital described as “the most quantitative and thorough examination of the action of metformin that we have seen outside of mice.”
But Rafael de Cabo, a translational geroscientist at the National Institute on Aging in Baltimore, pointed out that given only a few monkeys and the high cost of long-term primate experiments like this, it was concerning that the sample did not include female monkeys.
“While the impact and comprehensive mechanisms of metformin in primates have yet to be fully mapped, our findings indicate significant delays in the aging process,” the authors conclude.
Members of the Chinese research team have already launched a 120-person phase II clinical trial testing similar effects in humans in collaboration with a pharmaceutical company that makes metformin.
This research is published in
