Background Cytokines are signaling molecules operating within complex cascade patterns and having exceptional modulatory functions. They impact various physiological processes such as neuroendocrine and metabolic interactions, neurotrophins' metabolism, neuroplasticity, and may affect behavior and cognition. In our previous study, we found that sex and Cytomegalovirus (CMV)-serostatus may modulate levels of circulating pro- and anti-inflammatory cytokines, metabolic factors, immune cells, and cognitive performance, as well as associations between them. Results In the present study, we used a graph-theoretical approach to investigate the network topology dynamics of 22 circulating biomarkers and 11 measures of cognitive performance in 161 older participants recruited to undergo a six-months training intervention. For network construction, we applied coefficient of determination (R 2 ) that was calculated for all possible pairs of variables (N = 33) in four groups (CMV- men and women; CMV+ men and women). Network topology has been evaluated by clustering coefficient (CC) and characteristic path length (CPL) as well as local (E local ) and global (E global ) efficiency, showing the degree of network segregation (CC and E local ) and integration (CPL and E global ). We found that networks under consideration showed small-world networks properties with more random characteristics. Mean CC, as well as local and global efficiency were highest and CPL shortest in CMV- males (having lowest inflammatory status and highest cognitive performance). CMV- and CMV+ females did not show any significant differences. Modularity analyses showed that the networks exhibit in all cases highly differentiated modular organization (with Q-value ranged between 0.397 and 0.453). Conclusions In this work, we found that segregation and integration properties of the network were notably stronger in the group with balanced inflammatory status. We were also able to confirm our previous findings that CMV-infection and sex modulate multiple circulating biomarkers and cognitive performance and that balanced inflammatory and metabolic status in elderly contributes to better cognitive functioning. Thus, network analyses provide a useful strategy for visualization and quantitative description of multiple interactions between various circulating pro- and anti-inflammatory biomarkers, hormones, neurotrophic and metabolic factors, immune cells, and measures of cognitive performance and can be in general applied for analyzing interactions between different physiological systems.

中文翻译：

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循环生物标志物的网络拓扑动力学和老年巨细胞病毒血清阳性或血清阴性男性和女性的认知表现。

背景 细胞因子是在复杂的级联模式中运行并具有特殊调节功能的信号分子。它们影响各种生理过程，例如神经内分泌和代谢相互作用、神经营养因子的代谢、神经可塑性，并可能影响行为和认知。在我们之前的研究中，我们发现性和巨细胞病毒 (CMV) 血清状态可能会调节循环促炎和抗炎细胞因子、代谢因子、免疫细胞和认知能力的水平，以及它们之间的关联。结果 在本研究中，我们使用图论方法研究了 22 种循环生物标志物的网络拓扑动态和 161 名老年参与者的 11 项认知表现测量，这些参与者被招募来接受为期 6 个月的培训干预。对于网络建设，我们应用了为四组（CMV- 男性和女性；CMV+ 男性和女性）中所有可能的变量对 (N = 33) 计算的决定系数 (R 2 )。网络拓扑已通过聚类系数 (CC) 和特征路径长度 (CPL) 以及局部 (E local ) 和全局 (E global ) 效率进行评估，显示了网络隔离度 (CC 和 E local ) 和集成度 (CPL)和 E 全球）。我们发现正在考虑的网络显示出具有更多随机特征的小世界网络属性。CMV 男性的平均 CC 以及局部和全局效率最高，CPL 最短（炎症状态最低，认知能力最高）。CMV-和CMV+女性没有表现出任何显着差异。模块化分析表明，网络在所有情况下都表现出高度分化的模块化组织（Q 值介于 0.397 和 0.453 之间）。结论 在这项工作中，我们发现网络的分离和整合特性在炎症状态平衡的组中明显更强。我们还能够证实我们之前的发现，CMV 感染和性调节多种循环生物标志物和认知表现，并且老年人平衡的炎症和代谢状态有助于更好的认知功能。因此，网络分析提供了一种有用的策略，用于可视化和定量描述各种循环促炎和抗炎生物标志物、激素、神经营养和代谢因子、免疫细胞、