Metformin, an AMPK activator, can activate the NAD sirtuin pathway, leading to mitochondrial hormesis and increased NAD levels.

“Metformin will lower energy, inhibit mTOR. It will activate AMPK, obviously, we talked about that's what it's mainly doing, but it also raises NAD levels, which as we all know will activate the sirtuin.”

“Well, yeah, there's crosstalk between these various defenses. The AMPK pathway talks to the NAD sirtuin pathway. When you take metformin, and you get this mitochondrial hormesis, mitohormesis, that will raise NAD levels. It'll stimulate the production of the enzyme that turns NMN, a precursor of NAD, into NAD itself and raise NAD levels, and get the sirtuins active as well in the brain.”