A Review of Metformin's Anti-aging Mechanisms
Zixuan Zhao · Theoretical and Natural Science · 2025
Metformin is a frequently prescribed pharmaceutical for the therapeutic management of type 2 diabetes mellitus. Recent discoveries indicate that metformin possesses potential anti-aging properties, leading to further investigation of the mechanisms behind this action. This research examines the intrinsic processes by which metformin demonstrates its anti-aging effects, based on existing literature and data. The discourse commences with an exploration of the etiology of aging, succeeded by a comprehensive analysis of the fundamental mechanisms that underpin metformin's anti-aging properties. Subsequently, the paper reviews animal experiments related to metformin’s anti-aging properties, categorized into animal models and cellular models. Finally, the paper concludes with a discussion on non-core mechanisms of metformin, clinical trials, and future research directions. Metformin delays the aging process through direct or indirect activation of AMP-activated protein kinase (AMPK), which subsequently modulates multiple longevity-associated pathways. Specifically, it activates sirtuins (SIRTs), inhibits the mammalian target of rapamycin (mTOR) pathway, and suppresses NF-κB signaling. Additionally, metformin enhances the antioxidant response by promoting the activation of the Nrf2 pathway, thereby reducing reactive oxygen species (ROS) accumulation. Furthermore, it contributes to metabolic regulation by inhibiting gluconeogenesis. Together, these mechanisms collectively mediate metformin’s anti-aging effects.