Brain aging is associated with reduced cognitive function that increases the risk for dementia. Apigenin is a bioactive plant compound that inhibits cellular aging processes and could protect against age-related cognitive dysfunction, but its mechanisms of action in the brain have not been comprehensively studied. We characterized brain transcriptome changes in young and old mice treated with apigenin in drinking water. We observed improved learning/memory in old treated mice, and our transcriptome analyses indicated that differentially expressed genes with aging and apigenin were primarily related to immune responses, inflammation, and cytokine regulation. Moreover, we found that genes/transcripts that were increased in old vs. young mice but downregulated with apigenin treatment in old animals were associated with immune activation/inflammation, whereas transcripts that were reduced with aging but increased with apigenin were related neuronal function and signaling. We also found that these transcriptome differences with aging and apigenin treatment were driven in part by glial cells. To follow up on these in vivo transcriptome findings, we studied aged astrocytes in vitro, and we found that apigenin reduced markers of inflammation and cellular senescence in these cells. Collectively, our data suggest that apigenin may protect against age-related cognitive dysfunction by suppressing neuro-inflammatory processes.

大脑衰老与认知功能下降有关，从而增加患痴呆症的风险。芹菜素是一种生物活性植物化合物，可以抑制细胞衰老过程，并可以预防与年龄相关的认知功能障碍，但其在大脑中的作用机制尚未得到全面研究。我们表征了在饮用水中接受芹菜素处理的年轻和年老小鼠的大脑转录组变化。我们观察到老年治疗小鼠的学习/记忆能力得到改善，我们的转录组分析表明，衰老和芹菜素的差异表达基因主要与免疫反应、炎症和细胞因子调节有关。此外，我们发现，与年轻小鼠相比，老年小鼠中基因/转录本增加，但老年动物中芹菜素治疗下调的基因/转录本与免疫激活/炎症相关，而随着衰老而减少但芹菜素处理后转录本增加的基因/转录本与神经元功能和信号传导相关。 。我们还发现，这些转录组与衰老和芹菜素治疗的差异部分是由神经胶质细胞驱动的。为了跟进这些体内转录组发现，我们在体外研究了衰老的星形胶质细胞，我们发现芹菜素减少了这些细胞中炎症和细胞衰老的标志物。总的来说，我们的数据表明芹菜素可以通过抑制神经炎症过程来预防与年龄相关的认知功能障碍。