Background: Aging is accompanied by profound alterations in the central nervous system, among which neuroinflammation in the hippocampus is considered a major pathological hallmark. Chronic activation of the nuclear factor-kappa B (NF-κB) signaling pathway and the subsequent overproduction of pro-inflammatory cytokines, particularly interleukin-1 beta (IL-1β), contribute to impaired neural homeostasis, reduced neurogenesis, disrupted synaptic plasticity, and ultimately cognitive decline during aging. The present study aimed to compare the effects of eight weeks of moderate-intensity aerobic and resistance training on the hippocampal gene expression of NF-κB and IL-1β in aged male rats.





Methods: This experimental study employed a post-test-only design. Twenty-four 13-month-old male Wistar rats were randomly assigned to three groups (n = 8 per group): control, aerobic training, and resistance training. The aerobic training group performed treadmill running for eight weeks (five sessions per week) at progressive intensities ranging from 40% to 70% of maximal running velocity (Vmax). The resistance training group completed ladder-climbing exercise for the same duration and frequency at 60% of maximal voluntary carrying capacity (MVCC). Forty-eight hours after the final training session, the animals were deeply anesthetized and euthanized, and hippocampal tissues were collected. Relative gene expression of NF-κB and IL-1β was quantified using real-time quantitative polymerase chain reaction (RT-qPCR). Relative mRNA expression levels were calculated using the 2^-ΔΔCt method. Amplification specificity was confirmed by melt curve analysis. After confirming data normality and homogeneity of variances, statistical analyses were performed using one-way analysis of variance (ANOVA) followed by Tukey's post hoc test in SPSS version 26. Statistical significance was set at P < 0.05.





Results: Both aerobic and resistance training significantly reduced hippocampal NF-κB gene expression in aged rats. The mean expression level was significantly lower in the aerobic (0.432 ± 0.157) and resistance (0.626 ± 0.290) groups compared with the control group (1.010 ± 0.157) (P < 0.001). Likewise, IL-1β gene expression was significantly decreased in both exercise groups, with values of 0.514 ± 0.154 and 0.644 ± 0.227 in the aerobic and resistance training groups, respectively, compared with 1.015 ± 0.190 in the control group (P < 0.001). One-way ANOVA demonstrated significant effects of exercise intervention on the expression of NF-κB (F = 15.557, η² = 0.597, P < 0.001) and IL-1β (F = 14.492, η² = 0.580, P < 0.001), indicating large effect sizes. However, Tukey's post hoc analysis revealed no significant differences between the aerobic and resistance training groups for either NF-κB (P = 0.181) or IL-1β (P = 0.387). Furthermore, melt curve analysis showed a single distinct peak for each target gene, confirming amplification specificity and the absence of nonspecific products or primer-dimer formation.





Conclusion: The findings of this study demonstrate that eight weeks of moderate-intensity aerobic and resistance training are equally effective in downregulating the expression of the key neuroinflammatory genes NF-κB and IL-1β in the hippocampus of aged rats. These results suggest that both exercise modalities may attenuate age-related neuroinflammation through suppression of inflammatory signaling pathways, reduced microglial activation, and modulation of immune responses. Therefore, moderate-intensity aerobic and resistance exercise may serve as safe, accessible, and effective non-pharmacological strategies for mitigating neuroinflammation and preserving brain health during aging. Nevertheless, further investigations incorporating protein expression, cognitive function assessments, and additional molecular pathways are warranted to elucidate the underlying mechanisms more comprehensively.