Naito Kyoko, Akahori Hiromichi, Muto Yoshinori, Terada Tomoyoshi
United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
Department of Nursing, Faculty of Nursing and Rehabilitation, Chubu Gakuin University, 2-1 Kirigaoka, Seki 501-3993, Japan.
Genes (Basel). 2025 Aug 19;16(8):976. doi: 10.3390/genes16080976.
Frailty is an aging-associated syndrome involving a loss of physiological reserve and function, with decreased ability to recover from physical and psychosocial stress. However, the etiology and pathogenesis of frailty remain largely unknown.
This study aimed to investigate key genes involved in frailty pathogenesis, exercise effects, and their contributions.
We performed a weighted gene co-expression network analysis using a microarray dataset. By using the positive selection (PS), human accelerated region (HAR), and aging gene sets, we identified key genes for frailty and exercise-related genes.
We identified magenta and pink modules that have the most significant enrichments for the evolutionally elaborated genes. A functional enrichment analysis (FEA) revealed that genes related to redox-process regulation and extracellular-matrix organization were enriched in magenta and pink modules, respectively. We observed that six of the evolutionarily imprinted genes in the modules (, , , , and ) were highly connected and showed signs of hub properties, which might play crucial roles in frailty- and exercise-related mechanisms.
Further investigation into the functions of the identified modules and their member genes could aid in identifying diagnostic biomarkers and therapeutic targets for frailty.
衰弱是一种与衰老相关的综合征，涉及生理储备和功能的丧失，从身体和心理社会应激中恢复的能力下降。然而，衰弱的病因和发病机制在很大程度上仍不清楚。
本研究旨在调查参与衰弱发病机制、运动效应及其作用的关键基因。
我们使用一个微阵列数据集进行了加权基因共表达网络分析。通过使用正选择（PS）、人类加速区域（HAR）和衰老基因集，我们确定了衰弱的关键基因和运动相关基因。
我们确定了品红色和粉色模块，它们对进化精细基因的富集最为显著。功能富集分析（FEA）表明，与氧化还原过程调节和细胞外基质组织相关的基因分别在品红色和粉色模块中富集。我们观察到模块中的六个进化印记基因（、、、、和）高度连接并显示出枢纽特性的迹象，这可能在衰弱和运动相关机制中起关键作用。
进一步研究已确定模块及其成员基因的功能可能有助于识别衰弱的诊断生物标志物和治疗靶点。
