Sedentary individuals as “controls” in human studies: The correct approach?

Abstract

Recently in PNAS, Martin et al. (1) wrote a compelling review describing challenges in interpreting data from studies involving sedentary, overfed laboratory animals. These authors concluded that the use of sedentary animals as “controls” is problematic, and preclinical studies involving these animals may not be relevant to active, normal-weight humans. They argue that research from these investigations may “misinform the design and outcome of human studies,” highlighting aging-related investigations claiming an extension of lifespan by caloric restriction of ad libitum-fed laboratory animals. Therefore, investigators using rodent models should consider how levels of energy intake and exercise may affect experimental manipulations. We not only concur with these authors but contend that these same factors should be considered by scientists conducting translational studies using human participants.