Adolescent dietary restriction improves cognition and frailty in aged female Wistar rats

Dietary restriction (DR) is the most studied non-pharmacological intervention for extending both lifespan and healthspan. While previously considered universally beneficial, recent findings indicate that the effects of DR depend on its onset and duration. Although frequently practiced among teenage girls, the effects of DR in this developmental period remain insufficiently investigated, and existing conclusions are scarce. This study aims to determine the short- and long-term effects of mild adolescent DR on the behavior and frailty in aging female Wistar rats. Female Wistar rats were fed ad libitum (AL) or were dietary restricted (70% of AL daily intake) during early adolescence DR (EADR), middle adolescence DR (MADR), or both early and middle adolescence DR (EMADR). Short-term effects were examined using the Open Field (OF) and Y-maze tests, while long-term effects were assessed using OF, Y-maze, and Novel Object Recognition (NOR) tests, along with survival rate and frailty assessments. Long-term effects on cortical synaptic markers were examined by analyzing the expression of synaptophysin (SPH), drebrin, postsynaptic density protein 95 (PSD95), and phosphorylated PSD95 (p-PSD95). Despite the absence of early behavioral effects, predominantly beneficial effects on survival, behavior, frailty, followed by changes in synaptic proteins have been noticed at old age. Our results showed onset- and duration-dependent effects of adolescent DR on aged animals. This study is the first to evaluate the lifelong effects of adolescent DR and highlights the importance of early nutritional habits and the need for caution in dietary interventions during critical developmental stages.