Repeating the Point that Metformin Just Doesn't Look Good in Animal Studies
Based on studies conducted in mice, metformin is a terrible candidate drug for the treatment of aging. It may well benefit metabolically abnormal individuals, such as diabetics, but results for aged, metabolically normal mice are all over the map. Further, the gold standard, rigorous Interventions Testing Program found no benefit in their assessment. If the goal is to modestly slow aging, then rapamycin is way and far better: robust, replicated results on health and life span in animal studies. But the goal should not be to modestly slow aging! It should be to produce rejuvenation! The sizable fraction of academia and industry that is focused on altering metabolism to provoke greater stress responses and modestly slow aging will, unfortunately, most likely do little to reduce the suffering and death of old age.
The animal study most often cited as evidence that metformin slows aging in lab mice is no such evidence at all. The investigators tested two doses of metformin in healthy, wild-type, nonobese mice. At the lower of the two tested doses, metformin increased the animals' mean survival by a paltry 4-6%, and had no effect on maximum lifespan, meaning that the drug prevented a small number of deaths during and before middle age, but had no effect on aging. And when the mice were given the higher dose of metformin, it actually shortened the animals' lives!
The best animal study to test metformin as a potential anti-aging drug was conducted as part of the National Institute on Aging (NIA)'s Interventions Testing Program: a rigorous, systematic effort to test conventional "messing with metabolism" anti-aging agents. ITP studies are designed with several features that make them a better test than the great majority of studies of whether a potential longevity therapeutic actually works (in mice!). First, each time the ITP tests a potential longevity therapeutic, the lifespan study is done not just once, but three times independently in parallel, with three separate cohorts of mice living out their lives at three independent research sites, cared for by three different groups of scientists. Second, ITP tests all candidate longevity therapeutics in a healthy, genetically-diverse mouse population, which better resembles the normal human population than the genetically homogenous mouse strains widely used in biomedical research.
When the ITP researchers put metformin to the test, the result was unambiguous. It did not extend the lives of the mice at any site. It did not even cause the modest reduction in early deaths seen in the previous, widely-cited study. Metformin simply has no effect at all on lifespan in normal, healthy mice.
Link: https://www.sens.org/tame-attempt-slow-aging-part-1-metformin-in-mice/