AMPK activator O304 improves metabolic and cardiac function, and exercise capacity in aged mice

Age is associated with progressively impaired, metabolic, cardiac and vascular function, as well as reduced work/exercise capacity, mobility, and hence quality of life. Exercise exhibit positive effects on age-related dysfunctions and diseases. However, for a variety of reasons many aged individuals are unable to engage in regular physical activity, making the development of pharmacological treatments that mimics the beneficial effects of exercise highly desirable. Here we show that the pan-AMPK activator O304, which is well tolerated in humans, prevented and reverted age-associated hyperinsulinemia and insulin resistance, and improved cardiac function and exercise capacity in aged mice. These results provide preclinical evidence that O304 mimics the beneficial effects of exercise. Thus, as an exercise mimetic in clinical development, AMPK activator O304 holds great potential to mitigate metabolic dysfunction, and to improve cardiac function and exercise capacity, and hence quality of life in aged individuals. Ericsson et al. show in aged mice that the panAMPK activator O304 prevents and reverts age-associated hyperinsulinemia and insulin resistance, as well as improving cardiac function and exercise capacity. O304 thus functions as an exercise mimetic and could therefore have a similar therapeutic potential in aged humans and improve quality of life.