Intermittent Fasting Enhances Long Term Memory in Mice to a Greater Degree than Mild Calorie Restriction
It is always interesting to see studies that compare the outcomes of calorie restriction and intermittent fasting. In this case, researchers provide evidence to suggest that, at the same mild overall calorie reduction versus ad libitum feeding, intermittent fasting produces larger effects on memory function. If those effects are driven in large part by the biochemistry of hunger, then we might think that intermittent fasting produces more time spent hungry, and thus a larger effect size. The choice of amount of calorie reduction may well influence the outcome of any such comparison for other reasons, however.
Daily calorie restriction (CR) and intermittent fasting (IF) enhance longevity and cognition. Despite the positive effects of CR and IF in neurodegenerative and affective conditions, the specific behavioral contributions and mechanisms that differentiate both interventions remain largely unknown. Answering these questions is pivotal to adapting these regimens to human populations, given the challenges of adhering to a long-term CR regimen when compared to the improved adherence to variations of the IF paradigm.
Here, we directly compared the effects of IF to a matched 10% daily CR regimen upon learning and memory in mice. A 10% energy restriction protocol was chosen for the CR group following the observation that IF mice overall consume 10% less calories on a weekly basis. IF improved long-term retention memory to a greater extent than CR and was associated with increased adult hippocampal neurogenesis and upregulation of the longevity gene Klotho. Though klotho protein is produced primarily in the kidney, it is also highly expressed in some brain areas, including the dentate gyrus of the hippocampus and in particular by its mature neurons.
The function of klotho in the brain is still largely unknown but it has been proposed that it plays an important role in cognition because increased serum levels of klotho were associated with increased cognitive ability in humans and rodents. Here, we confirm previous evidence suggesting that Kl is an important regulator of adult hippocampal neurogenesis and propose it as a novel molecular player through which IF may enhance cognitive performance.