The Anti-Aging Mechanism of Metformin: From Molecular Insights to Clinical Applications

Aging represents a complex biological phenomenon marked by the progressive deterioration of physiological functions over time, reduced resilience, and increased vulnerability to age-related diseases, ultimately culminating in mortality. Recent research has uncovered diverse molecular mechanisms through which metformin extends its benefits beyond glycemic control, presenting it as a promising intervention against aging. This review delves into the anti-aging properties of metformin, highlighting its role in mitochondrial energy modulation, activation of the AMPK-mTOR signaling pathway, stimulation of autophagy, and mitigation of inflammation linked to cellular aging. Furthermore, we discuss its influence on epigenetic modifications that underpin genomic stability and cellular homeostasis. Metformin's potential in addressing age-associated disorders including metabolic, cardiovascular, and neurodegenerative diseases is also explored. The Targeting Aging with Metformin (TAME) trial aims to provide key evidence on its efficacy in delaying aging in humans. Despite these promising insights, significant challenges persist in gaining a more comprehensive understanding into its underlying mechanisms, determining optimal dosing strategies, and evaluating long-term safety in non-diabetic populations. Addressing these challenges is crucial to fully realizing metformin's potential as an anti-aging therapeutic.