METFORMIN-ENHANCES RESILIENCE VIA HORMESIS.

The present paper demonstrates that metformin (MF) induced a broad spectrum of hormetic biphasic dose response in a wide range of experimental studies, affecting multiple organ systems, cell types, and endpoints enhancing resilience to chemical stresses in preconditioning and co-current exposure protocols. Detailed mechanistic evaluations indicate that MF-induced hormetic-adaptive responses are mediated often via the activation of adenosine monophosphate-activated kinase (AMPK) protein and its subsequent upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2). Hormesis-induced protective responses by MF are largely mediated via a vast and highly integrated anti-inflammatory molecular network that enhances longevity and delays the onset and slows the progression of neurodegenerative and other chronic diseases.