Translation Goes Both Ways: The Power of Reverse Translation from Human Trials into Animal Models

Much attention has been given to “translational research” with the assumption that such models follow a stepwise progression from basic/discovery science at the bench to application at the bedside. This practice ignores the valuable reverse aspect of translational research (i.e., “reverse translation”) where discoveries or observations at the bedside can inform and stimulate more mechanistic, basic work back at the bench, which in turn should expedite clinical applicability. This commentary reflects on the current thinking regarding reverse translation, with particular emphasis on the value of reverse translational design in understanding acute responses and chronic adaptations to exercise. Overall, we conclude that reverse translational designs offer a powerful avenue of investigation that should be fully leveraged to maximize impact on the understanding and treatment of human disease.