- Physical exercise and fitness have been proposed as potential factors that promote healthy cognitive aging. Some of the support for this hypothesis has come from animal research. Animal studies are also used to propose the physiological mechanisms underlying the cognitive performance improvement associated with exercise. In the present review and meta-analysis, we discuss several methodological problems that limit the contribution of animal studies to the understanding of the putative effects of exercise on cognitive aging. We suggest that the most likely measure to equate exercise intensity in rodent and humans may be oxygen consumption (VO2) because observed values are surprisingly similar in young and older rodents and humans. For practical reasons, several animal studies use young rodents kept in social isolation. We show that social isolation is associated with an enhanced impact of exercise on cognitive performance but not on some physiological measures thought to mediate the effect of exercise. Surprisingly, two months or more of exercise intervention appeared to be ineffective to promote cognitive performance compared to shorter durations. We argue that impact of exercise in socially isolated animals is explained by an alleviation of environmental impoverishment as much as an effect of physical exercise. It is possible that the introduction of exercise in rodents is partly mediated by environmental changes. It may explain why larger effects are observed for the shorter durations of exercise while much smaller effects are found after longer periods of exercise.