As the only paradigm that has consistently increased life span and inhibited the onset and/or progression of disease, dietary restriction has multiple effects on a variety of organ systems. In this brief review, the goal of the panel was to attempt to understand the role of changes in physical activity and body composition as possible modulators of the life span in experimental animals and humans. We focus on whether changes in exercise behavior and body composition produce similar changes as those found in dietary restriction and whether these changes can be used to either replace or enhance the beneficial effects of dietary restriction. The complexity of the two stimuli is emphasized in our report, with suggestions offered on how to better interpret existing research. Our panel briefly examines evidence in experimental animals and humans about the specific contributions of each of these factors to altering life span and age-related pathologies. We also discuss additional animal studies and/or human intervention studies that could be performed to clarify these issues. Finally, we provide suggested avenues for future research in this area of changes in physical activity and body composition as dietary restriction mimetics.