摘要： Human neurons are functional over an entire lifetime，yet the mechanisms that preserve function and protect against neurodegeneration during aging are unknown. Here we performed a system-level study on human brain aging by weighted gene co-expression network analysis（ WGCNA） to identify significant modules in the network，and followed by functional and pathway enrichment analyses. Moreover，hub genes in the module were analyzed by network feature selection. As a result，nineteen distinct gene modules were identifi ed，and six modules showed signifi cant associations with the status of brain aging. After network feature analysis，the blue and magenta modules demonstrated a remarkably correlation with human brain aging progression. The top hub genes with high connectivity or gene signifi cance in the blue module were ultimately determined，including CA10，ACTR3B，JAZF1 and MFSD4A. These genes were further verifi ed in clinical samples. Finally，the potential regulators of blue module were characterized. These fi ndings highlighted a module and affi liated genes as playing important roles in the regulation of normal brain aging，which may point to potential targets for therapeutic interventions.