Metformin, a drug commonly used to treat type 2 diabetes, has been found to extend healthspan and lifespan in male mice when administered at a low dose (0.1% w/w in the diet) starting at middle age. Higher doses (1% w/w) were toxic. Metformin mimics some of the benefits of calorie restriction, such as improved physical performance, increased insulin sensitivity, and reduced low-density lipoprotein and cholesterol levels without a decrease in caloric intake. At the molecular level, metformin increases AMP-activated protein kinase (AMPK) activity and enhances antioxidant protection, leading to reduced oxidative damage accumulation and chronic inflammation. These findings suggest that metformin may promote healthy aging and raise the possibility of metformin-based interventions to extend lifespan and improve healthspan.Metformin, a drug commonly used to treat type 2 diabetes, has been found to extend healthspan and lifespan in male mice when administered at a low dose (0.1% w/w in the diet) starting at middle age. Higher doses (1% w/w) were toxic. Metformin mimics some of the benefits of calorie restriction, such as improved physical performance, increased insulin sensitivity, and reduced low-density lipoprotein and cholesterol levels without a decrease in caloric intake. At the molecular level, metformin increases AMP-activated protein kinase (AMPK) activity and enhances antioxidant protection, leading to reduced oxidative damage accumulation and chronic inflammation. These findings suggest that metformin may promote healthy aging and raise the possibility of metformin-based interventions to extend lifespan and improve healthspan.