For years, biohackers have been using off-label drugs to prolong their lives. One of these drugs, the popular diabetes medication metformin, has also caught the attention of those who experiment on sample sizes greater than one. In a new review published in the journal Aging, researchers from Hamad Bin Khalifa University in Qatar investigated the potential anti-aging effects of metformin by surveying cellular studies, animal model research, and human observational investigations.
On a cellular level, they found that metformin increases autophagy (how cells recycle damaged parts), boosts mitochondria production, and reduces oxidative stress. It also seems to help with other negative aging hallmarks, including deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence (when aging cells stop dividing), and more. They discovered associations between metformin and reduced epigenetic age acceleration as well. Still, they caution that these molecular and cellular changes may not translate to an increased lifespan.
Read more: “Is Immortality Possible?”
In animal studies, the drug seemed to offer more promise. Experiments involving roundworms and multiple mouse models showed metformin lengthens lifespans, and male macaques showed reduced aging markers in their tissues. (Which is great news if you’re a biohacking roundworm, mouse, or male macaque).
Human observational studies are a different story. While they also showed metformin could produce better survival and healthier aging, there were a couple caveats. For starters, because metformin is a diabetes drug, most of the subjects being researched are people with the illness. Additionally, the endpoints of the investigations varied wildly—from mortality to frailty—all lumped under the “aging” umbrella. According to the team, this makes it tough to figure out if metformin slows aging or just improves disease outcomes in certain groups.
Observational studies are one thing, but what about clinical trials? There are at least two. In one, older people (between the ages of 50 and 79) with metabolic syndromes were randomly given metformin or a placebo. The drug protected against diabetes, but not cancer, cardiovascular disease, or mortality. Another clinical trial involving 3,000 healthy older adults began in 2017, but no results have been published yet.
“The forward challenge will be to identify populations, biological pathways, and outcome measures through which metformin will meaningfully delay age-related functional decline, thus turning its metabolic benefits into actionable schemes for healthy aging,” the researchers concluded.
The bottom line is: Metformin seems to help with the hallmarks of aging at a cellular level via well-understood pathways. Whether those benefits translate to a longer lifespan is still up in the air.
So biohacker beware. 
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