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

Abstract

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.

• Authors: Madelene Ericsson, Pär Steneberg, Rakel Nyrén, Helena Edlund
• Journal: Communications biology (Commun Biol) Vol. 4 Issue 1 Pg. 1306 (11 18 2021) ISSN: 2399-3642 [Electronic] England
• PMID: 34795407 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (genetics, metabolism)
• Age Factors
• Animals
• Disease Models, Animal
• Exercise Tolerance (genetics)
• Heart (physiology)
• Humans
• Insulin Resistance (genetics)
• Male
• Mice (genetics, metabolism, physiology)
• Physical Conditioning, Animal