Effects of moderate and high intensity exercise on mitokine and cognitive function in hippocampus tissue of D-gal-induced aging rat model

Mitokines play a critical role in maintaining cognitive function and promoting healthy aging by modulating systemic responses to cellular stress. This study examined the effects of three exercise modalities, including Sprint Interval Training (SIT), High-Intensity Interval Training (HIIT), and Moderate-Intensity Continuous Training (MICT), on mitokine expression and cognitive performance in the d-galactose-induced aging rat model. A total of 35 male Wistar rats were included: 7 as healthy control, and 28 received d-galactose (150 mg/kg/day for 8 weeks) then randomly divided into d-gal, MICT, HIIT, and SIT (n = 7 each). Exercise training was performed five days per week for eight weeks. Protocols included HIIT (85% vVO₂max), MICT (60% vVO₂max), and SIT (4-9 × 10 s at 118-165% vVO₂max). FGF21 and GDF15 protein levels were measured by Western blotting. Cognitive function was evaluated using the passive avoidance test, and histological changes were assessed via H&E staining. The results demonstrated that HIIT markedly elevated FGF21 protein expression compared to both the d-gal and other exercise groups (p < 0.0001), suggesting superior mitochondrial and metabolic adaptation. In contrast, the d-galactose group exhibited the highest levels of GDF15, with significant reductions observed in the HIIT and MICT groups relative to SIT. All exercise protocols led to a significant increase in step-through latency (p < 0.0001) and a marked reduction in the time spent in the dark chamber (p < 0.0001), both indicative of improved aversive memory in the passive avoidance task. These findings support the notion that HIIT optimally modulates mitokine activity to promote mitochondrial health and cognitive function. In addition to molecular adaptations, behavioral improvements such as enhanced memory performance further underscore exercise as a viable strategy for mitigating age-related impairments.