Metformin, a widely used drug for type 2 diabetes, was shown to extend healthspan and lifespan in male mice when administered starting at middle age. At a dose of 0.1% (w/w) in the diet, metformin improved physical performance, increased insulin sensitivity, and reduced low-density lipoprotein and cholesterol levels without decreasing caloric intake. It also increased AMP-activated protein kinase (AMPK) activity and antioxidant protection, reducing oxidative damage and chronic inflammation. However, a higher dose (1% w/w) was toxic and shortened lifespan. Metformin mimics some effects of calorie restriction, including improved metabolic health and reduced inflammation. The study found that metformin treatment led to a 5.83% extension of mean lifespan in C57BL/6 mice, while the higher dose significantly reduced lifespan. Metformin also improved physical performance, delayed age-related cataracts, and reduced markers of metabolic syndrome. At the molecular level, metformin induced a gene expression profile similar to that of calorie restriction, suggesting it may mimic some of the beneficial effects of calorie restriction. Metformin also activated the Nrf2-dependent antioxidant response, which is involved in reducing oxidative stress and inflammation. The study highlights the potential of metformin as a therapeutic agent for promoting healthy aging.Metformin, a widely used drug for type 2 diabetes, was shown to extend healthspan and lifespan in male mice when administered starting at middle age. At a dose of 0.1% (w/w) in the diet, metformin improved physical performance, increased insulin sensitivity, and reduced low-density lipoprotein and cholesterol levels without decreasing caloric intake. It also increased AMP-activated protein kinase (AMPK) activity and antioxidant protection, reducing oxidative damage and chronic inflammation. However, a higher dose (1% w/w) was toxic and shortened lifespan. Metformin mimics some effects of calorie restriction, including improved metabolic health and reduced inflammation. The study found that metformin treatment led to a 5.83% extension of mean lifespan in C57BL/6 mice, while the higher dose significantly reduced lifespan. Metformin also improved physical performance, delayed age-related cataracts, and reduced markers of metabolic syndrome. At the molecular level, metformin induced a gene expression profile similar to that of calorie restriction, suggesting it may mimic some of the beneficial effects of calorie restriction. Metformin also activated the Nrf2-dependent antioxidant response, which is involved in reducing oxidative stress and inflammation. The study highlights the potential of metformin as a therapeutic agent for promoting healthy aging.