Targeting ageing and preventing organ degeneration with metformin

Ageing is characterized by a decline in cognitive and bodily functions. Metformin, the most commonly prescribed antidiabetic agent today, has proved to be able to modulate oxidative stress, several inflammatory pathways and cellular senescence to promote anti-ageing. This review aims to explore and summarize the effects of metformin on ageing.

Metformin, a longstanding treatment for diabetes, has been shown to increase lifespan in both vertebrate and mammalian models. This pleiotropic effect is hypothesized to mimic calorie restriction, a currently proven means of slowing ageing, by decreasing insulin and insulin-like growth factor (IGF)-1 levels and improving insulin sensitivity. However, studies have shown that metformin is also able to target several other ageing pathways, thereby inhibiting mammalian target of rapamycin (mTOR), increasing AMPK activity and improving DNA repair. Clinical studies, such as those supported by the UK Clinical Practice Research Datalink service, have reported that diabetes patients treated with metformin live longer than patients without diabetes. Metformin use can also reduce type 2 diabetes mellitus (T2DM) incidence among those at risk, lower cancer incidence, and improve cognitive function, cardiovascular disease (CVD) risk factors and atherosclerosis.

Various studies have found that metformin can target several nutrient-sensing, anti-ageing and immune pathways, leading to reductions in oxidative stress, inflammation and DNA damage as well as providing effects similar to those of calorie restriction. However, further trials are still needed to confirm these findings.