Polyphenol Supplementation Reverses Age-Related Changes in Microglial Signaling Cascades.
Polyphenol Supplementation Reverses Age-Related Changes in Microglial Signaling Cascades.
复制标题
DOI：
10.3390/ijms22126373
复制
发表时间：
2021-06-14
影响因子：
5.6
通讯作者：
Bickford PC
中科院分区：
文献类型：
--
作者：
Jalloh A;Flowers A;Hudson C;Chaput D;Guergues J;Stevens SM Jr;Bickford PC
衰老神经免疫系统中的小胶质细胞活性是衰老相关功能障碍的核心参与者。衰老通过蛋白质信号级联的变化改变小胶质细胞的功能。这些转变可以传播神经退行性病理学。治疗需要多方面的方法来理解和解决这一过程的随机性。多酚提供了一种纠正与年龄相关的衰退的方法。我们的小组使用质谱（MS）分析来解释这些老化小胶质细胞通路的复杂性质。在我们的第一个实验中，我们比较了从年轻和老年大鼠中分离出的原代小胶质细胞，并鉴定了这些组之间 197 个显着差异表达的蛋白质。然后，我们进行了生物信息学分析，以探索与小胶质细胞稳态和功能随年龄相关的典型信号级联的差异。在第二个实验中，我们研究了老年动物在膳食补充 NT-020（一种多酚混合物）30 天后这些途径的变化。我们通过 MS 分析确定了 NT-020 组和对照饮食组之间 144 个差异表达的蛋白质。生物信息学分析预测 NT-020 驱动控制炎症、细胞代谢和蛋白质稳态的年龄相关经典途径上调的逆转。我们的结果强调了小胶质细胞衰老在蛋白质相互作用水平上的显着方面，并证明了多酚作为年龄相关功能障碍治疗剂的潜在作用。
Microglial activity in the aging neuroimmune system is a central player in aging-related dysfunction. Aging alters microglial function via shifts in protein signaling cascades. These shifts can propagate neurodegenerative pathology. Therapeutics require a multifaceted approach to understand and address the stochastic nature of this process. Polyphenols offer one such means of rectifying age-related decline. Our group used mass spectrometry (MS) analysis to explicate the complex nature of these aging microglial pathways. In our first experiment, we compared primary microglia isolated from young and aged rats and identified 197 significantly differentially expressed proteins between these groups. Then, we performed bioinformatic analysis to explore differences in canonical signaling cascades related to microglial homeostasis and function with age. In a second experiment, we investigated changes to these pathways in aged animals after 30-day dietary supplementation with NT-020, which is a blend of polyphenols. We identified 144 differentially expressed proteins between the NT-020 group and the control diet group via MS analysis. Bioinformatic analysis predicted an NT-020 driven reversal in the upregulation of age-related canonical pathways that control inflammation, cellular metabolism, and proteostasis. Our results highlight salient aspects of microglial aging at the level of protein interactions and demonstrate a potential role of polyphenols as therapeutics for age-associated dysfunction.
登录
查看更多内容
影响因子：
5.1
作者：
Fu, Ruying;Shen, Qingyu;Xu, Pengfei;Luo, Jin Jun;Tang, Yamei
通讯作者：
Tang, Yamei
影响因子：
6.2
作者：
Durafourt, Bryce A.;Moore, Craig S.;Antel, Jack P.
通讯作者：
Antel, Jack P.
影响因子：
9.3
作者：
Flowers A;Bell-Temin H;Jalloh A;Stevens SM Jr;Bickford PC
通讯作者：
Bickford PC
影响因子：
3.7
作者：
Gu HF;Nie YX;Tong QZ;Tang YL;Zeng Y;Jing KQ;Zheng XL;Liao DF
通讯作者：
Liao DF
影响因子：
3.3
作者：
Frank MG;Barrientos RM;Watkins LR;Maier SF
通讯作者：
Maier SF