The anti-aging role of metformin, clinical applications to pursue the longevity road

Background Metformin, an oral antidiabetic drug widely used for over 60 years, has been recognized for its safety and effectiveness in the treatment of Type-2 Diabetes Mellitus (T2DM). In addition to the anti-diabetic properties, recent studies have shed light on its anti-aging, healthspan and longevity promoter potentials. This review aims to explore the anti-aging role of metformin and identify its unconventional fields of application. Methods A systematic review was conducted using the PubMed (MEDLINE) library from January 2001 to July 2023, focusing on terms related to plastic surgery, aesthetic surgery, anti-aging, rejuvenation, lifespan, healthspan, anti-inflammatory, aesthetic medicine, and metformin. Eligibility criteria included original studies addressing metformin as anti-aging and healthspan-promoting therapies in humans. Results The final synthesis included 29 articles categorized by topic into studies on the mechanisms underlying the anti-aging effects of metformin and studies on its potential therapeutic applications. Metformin, by activating 5’-AMP-activated protein kinase (AMPK), appears to influence cellular aging, oxidative stress, gut microbiota and epigenetics, potentially resulting in anti-aging effects. Furthermore, the present review includes evidence for the role of metformin in age-related diseases, such as cardiovascular disease (CVD) and neurodegeneration, suggesting potential benefits in preventing CVDs and preserving cognitive functions. Moreover, despite controversial data, metformin may also have an influence on cancer. Conclusions Metformin is an effective drug in both diabetic and pre-diabetic patients. Moreover, it appears to exert multiple preventive actions, potentially resulting in an anti-aging drug, influencing both episodic and linear components of aging with promising off-label applications. In consideration of its well-established safety profile, future research should explore its implications also in healthy populations. Level of Evidence Not gradable.