A comprehensive study published in Cell found that long-term use of metformin slowed the aging process in monkeys. The researchers found that the monkeys given metformin had approximately a 6-year reduction in brain age over the 40-month study. Metformin also protected brain health and cognition.
Metformin and aging
The normal aging process involves the impact of increasing tissue and physiological dysfunction, often including cardiovascular, diabetic, and brain disorders. Many compounds have been tested to evaluate their ability to slow aging and expand the “healthspan” of humans. Metformin, a drug used for more than 60 years to treat type 2 diabetes, is a promising candidate.
Previous studies have shown that in addition to being an inexpensive and safe medication, metformin slows physiological aging in animal models such as worms, fruit flies, and rodents. However, results have been inconclusive in human studies (see background on our webpage on metformin and aging).
The recent study led by scientists from China made use of new tools for gauging biological aging at the molecular level. This enabled them to create aging clocks to determine the effectiveness of metformin on numerous aging parameters.
Physical and psychological outcomes
The study involved male macaque monkeys aged 13-16 years (approximately equivalent to 40-50 human years). One group received 20 mg/kg of metformin, and the other received a placebo for 1200 days (approximately 3.3 years, equivalent to about 10 human years). Additionally, the study included younger and middle-aged monkeys for comparison.
This elegant research project involved the evaluation of many biological processes to pinpoint changes in the body and the molecular mechanisms behind those changes. Sixty-eight biological parameters were measured throughout the study, including body shape indicators such as BMI, blood tests, and imaging studies (computed tomography [CT] scans and magnetic resonance imaging [MRI]). The monkeys even participated in a battery of psychological tests to measure brain health, including memory, learning, and cognitive flexibility tasks.
Metformin proved to be safe for the monkeys, and they did not lose weight or have any blood glucose problems. The metformin group had less aging-associated periodontal bone loss than the control group.
Metformin’s effect on the brain and cognition
Cognitive testing found that the metformin-treated monkeys had better memory retention, learning ability, and enhanced cognitive resilience. Data from brain MRI and tissue evaluation showed that the frontal lobe cortical area was thicker in the metformin group. This brain area is important for cognitive function and normally becomes thin with aging. There was also some evidence of increased thickness in the parietal lobe.
The authors concluded, “Taken together, these findings, in conjunction with enhancements in memory and cognitive function, suggest that metformin might postpone aging-associated structural deterioration of the brain, particularly in the frontal lobe.”
The molecular impacts of metformin on monkey tissue
Metformin was also found to reverse aging in many other tissues, such as the lungs, kidneys, liver, skin, and muscles. The evaluation of metformin at the molecular level provided evidence for the following health impacts:
- Metformin “rescued” most aged tissues.
- Metformin reduced the emergence of aging hallmarks, including tissue degeneration and inflammation.
- Metformin slowed liver aging and protected liver function, potentially by enhancing the metabolic functions of liver cells.
- Metformin slowed the aging of brain neurons and overall brain aging, largely through a potent cellular antioxidant, the Nrf2 pathway activation.
Evaluating biological age calculated through an aging clock showed that monkeys treated with metformin were approximately 6 years younger.
Is metformin an anti-aging powerhouse?
The comprehensive monkey study certainly points to metformin as a compound capable of slowing aging indicators and preserving brain structure and function. The authors concluded that their research paves the way for advancing pharmaceutical strategies against human aging — and have already initiated a human clinical trial to test their findings. Other clinical studies on metformin are underway as well. These trials will help to determine if the same effects are found in humans as in the monkey study, and determine long-term safety for non-diabetic users.
To learn more about the various effects that metformin has on human health, take a look at our metformin page.
