Results: Eight CS-related genes were identified as key gene signatures in MCI group, which were mainly enriched in the regulation of response to DNA damage stimulus, Sin3 complex and transcription corepressor activity. The hub gene-drug network, hub gene-miRNA network as well as transcription factor-gene regulatory network were used to analyze potential therapeutic targets for MCI. The protein–protein interaction network was used to extract hub genes and the logistic regression was performed to distinguish the MCI patients from controls. Then, pathway and GO enrichment analyses were performed to further elucidate the mechanism of MCI. The differentially expressed CS-related genes would be obtained through overlapping among the above datasets. Weighted gene co-expression network analysis (WGCNA) was conducted to discover the key relationships behind the co-expression modules. Methods: The mRNA expression profiles of peripheral blood samples from patients in MCI and non-MCI group were download from gene expression omnibus (GEO) database (GSE63060 for training and GSE18309 for external validation), CS-related genes were obtained from CellAge database. This study aims to explore biomarkers and potential therapeutic targets in MCI based on CS. Cellular senescence (CS) is a stress response that accompanies permanent cell-cycle arrest, which has been reported to be a fundamental pathological mechanism of many age-related diseases. 5Tianjin Institute of Hepatobiliary Disease, Tianjin, Chinaīackground: Mild cognitive impairment (MCI), a syndrome defined as decline of cognitive function greater than expected for an individual’s age and education level, occurs in up to 22.7% of elderly patients in United States, causing the heavy psychological and economic burdens to families and society.4Artificial Cell Engineering Technology Research Center, Tianjin, China. ![]() 3Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China.2Department of Anesthesiology, The First People’s Hospital of Shangqiu, Shangqiu, Henan, China.1Department of Anesthesiology, The Third Central Clinical College of Tianjin Medical University, Tianjin, China.Songmei Ma 1,2 †, Tong Xia 1 †, Xinyi Wang 1,3,4,5 and Haiyun Wang 1,3,4,5 *
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