[Alex3917]

> the leap from "mitochondrial complex I inhibition is associated with PSP" to "metformin causes PSP" is unwarranted

The mechanism of action is relatively straightforward: the inhibition is caused by a building up oxides within the mitochondria, which makes them less efficient at producing energy. And if the mitochondria go long enough without a mitochondrial antioxidant clearing out the oxides, they eventually die. And if enough of the mitochondria within your brain die, you get PSP.

My best guess as to the reason we haven't seen an association between PSP and metformin is that metformin is actually a mitochondrial type I adaptogen rather than a mitochondrial type I inhibitor. I'm definitely not telling people not to take it, but if you are then I think setting a couple Google scholar alerts would be prudent.