A new study published in Cell demonstrates that metformin, a widely used drug for Type 2 diabetes, can slow down aging processes in elderly monkeys. The research, which monitored the physical and cognitive health of male macaques over three years, suggests that metformin could have significant potential for extending human healthspan.
The study involved administering daily metformin pills to monkeys aged the equivalent of 52 to 64 human years. Compared to a control group of naturally aging monkeys, those treated with metformin showed preserved learning and memory abilities, reduced brain shrinkage, and a restoration of neurons to a more youthful state. The "brain age" of the treated monkeys was dialed back by almost 6 years, or around 18 human years.
Broad Anti-Aging Effects
Beyond the brain, metformin's effects were observed in multiple tissues. The drug reduced chronic inflammation, a hallmark of aging, and slowed liver aging. Cellular mechanisms that protect the liver were also boosted. Kidneys, lungs, and muscles were "rescued" from age-related problems, with their gene expression profiles reverting to more youthful ones. These findings bridge the gap between previous studies in rodents and this primate model, strengthening the evidence for metformin's anti-aging potential.
Dr. Alex Soukas at Massachusetts General Hospital, who was not involved in the study, noted that this is the "most quantitative, thorough examination of metformin action that I’ve seen beyond mice."
Metformin's Mechanism and History
Metformin, derived from the plant goat's rue, has been used to treat Type 2 diabetes for decades. It works through multiple molecular pathways to control cell growth, metabolism, and inflammation, all of which are implicated in aging. Epidemiological studies have previously indicated that metformin reduces the risk of cancer and dementia in humans. A 2014 study of 78,000 people found that individuals with Type 2 diabetes on metformin lived longer, on average, than those of the same age who did not have diabetes and did not take the drug.
Study Details and Limitations
The monkey study involved comprehensive physical exams, including 65 health measures such as BMI, blood tests, and brain imaging. Cognitive tests assessed memory, learning, and flexible thinking. The team watched the monkeys’ health for over three years, collecting gene expression and protein data from multiple organs and tissues.
Researchers validated their findings by examining tissues under a microscope, observing a decrease in senescent cells and reduced scarring in the lungs, kidneys, and heart. Metformin also slashed chronic inflammation throughout the body.
While the results are promising, the study has limitations. The sample size was small, with only 12 monkeys receiving the drug. The study also only tested metformin in males. Further research is needed to replicate the findings in a larger population and to include female subjects, given that aging trajectories and health measurements differ between sexes.
Future Directions
The research team plans to expand their study by following the monkeys for a longer period to assess whether metformin increases lifespan. They also intend to investigate whether the anti-aging effects persist after treatment is stopped. Further studies are also underway to clarify the exact mechanisms by which metformin works in the aging body.
Metformin has already garnered the attention of the FDA. The agency approved the TAME (Targeting the Biology of Aging) trial in 2015, which aims to recruit 3,000 elderly people to further investigate metformin's anti-aging effects. Additionally, the authors have launched a smaller, placebo-controlled clinical trial to assess whether the drug slows aging in middle-aged to elderly males.
