The evidence for metformin to even modestly slow aging is not robust, certainly not when compared to the evidence for rapamycin. The mouse lifespan data for metformin treatment is all over the map, and the human data in diabetic patients has issues. Still, some studies show benefits, including the recently published non-human primate study noted here. One critique is that the researchers developed novel aging clocks to assess biological age, rather than use a standard mammalian clock, but one can’t argue with the data on cognitive function and potential protective mechanisms.
Metformin has been used for more than 60 years to lower blood-sugar levels in people with type 2 diabetes – and is the second most-prescribed medication in the United States. The drug has long been known to have effects beyond treating diabetes, leading researchers to study it against conditions such as cancer, cardiovascular disease, and ageing. Data from worms, rodents, flies and people who have taken the drug for diabetes suggest the drug might have anti-ageing effects. But its effectiveness against ageing had not been tested directly in primates, and it is unclear whether its potential anti-ageing effects are achieved by lowering blood sugar or through a separate mechanism.
This led researchers to test the drug on 12 elderly male cynomolgus macaques (Macaca fasciucularis); another 16 elderly monkeys and 18 young or middle-aged animals served as a control group. Every day, treated monkeys received the standard dose of metformin that is used to control diabetes in humans. The animals took the drug for 40 months, which is equivalent to about 13 years for humans. Over the course of the study, researchers took samples from 79 types of the monkeys’ tissues and organs, imaged the animals’ brains and performed routine physical examinations. By analysing the cellular activity in the samples, the researchers were able to create a computational model to determine the tissues’ ‘biological age’, which can lag behind or exceed the animals’ age in years since birth.
The researchers observed that the drug slowed the biological ageing of many tissues, including from the lung, kidney, liver, skin and the brain’s frontal lobe. They also found that it curbed chronic inflammation, a key hallmark of ageing. The study was not intended to see whether the drug extended the animals’ lifespans; previous research has not established an impact on lifespan but has shown lengthened healthspan – the number of years an organism lives in good health. The researchers also identified a potential pathway by which the drug protects the brain: it activates a protein called NRF2, which safeguards against cellular damage triggered by injury and inflammation.
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