Metformin-enhances resilience via hormesis

Area of Science:

• Pharmacology
• Cell Biology
• Toxicology

Background:

• Metformin (MF) is widely used for type 2 diabetes.
• Hormesis, a biphasic dose response, suggests low-dose stimulation and high-dose inhibition.
• The hormetic effects of MF across diverse biological systems require further elucidation.

Purpose of the Study:

• To demonstrate that metformin induces hormetic biphasic dose responses.
• To investigate the underlying molecular mechanisms of MF-induced hormesis.
• To explore the potential of MF-induced hormesis in enhancing resilience and combating chronic diseases.

Main Methods:

• Review and synthesis of experimental studies on metformin's effects.
• Mechanistic evaluations focusing on key signaling pathways.
• Analysis of MF's impact on cellular and organ system responses to stress.

Main Results:

• Metformin (MF) induced a broad spectrum of hormetic biphasic dose responses.
• MF enhanced resilience to chemical stresses in various experimental models.
• Mechanisms involve activation of adenosine monophosphate-activated kinase (AMPK) and nuclear factor erythroid 2-related factor 2 (Nrf2).

Conclusions:

• Metformin-induced hormesis is mediated by AMPK and Nrf2 activation.
• These adaptive responses involve an integrated anti-inflammatory network.
• MF-induced hormesis enhances longevity and delays chronic disease progression, including neurodegenerative diseases.