Transcriptomic analysis of mRNAs in human whole blood identified age-specific changes in healthy individuals

Abstract

Older age is one of the most important shared risk factors for multiple chronic diseases, increasing the medical burden to contemporary societies. Current research focuses on identifying aging biomarkers to predict aging trajectories and developing interventions aimed at preventing and delaying the progression of multimorbidity with aging. Here, a transcriptomic changes analysis of whole blood genes with age was conducted. The age-related whole blood gene-expression profiling datasets were downloaded from the Gene Expression Omnibus (GEO) database. We screened the differentially expressed genes (DEGs) between healthy young and old individuals and performed functional enrichment analysis. Cytoscape with Cytohubba and MCODE was used to perform an interaction network of DEGs and identify hub genes. In addition, ROC curves and correlation analysis were used to evaluate the accuracy of hub genes. In total, we identified 29 DEGs between young and old samples that were enriched mainly in immunoglobulin binding and complex, humoral immune response, and immune response-activating signaling pathways. In combination with the PPI network and topological analysis, 4 hub genes (IGLL5, Jchain, POU2AF1, and Bach2) were identified. Pearson analysis showed that the expression changes of these hub genes were highly correlated with age. Among them, 3 hub genes (IGLL5, POU2AF1, and Bach2) were identified with good accuracy (AUC score > 0.7), indicating that these genes were the best indicators of age. Together, our results provided potential biomarkers IGLL5, POU2AF1, and Bach2 to identify individuals at high early risk of age-related disease to be targeted for early interventions and contribute to understanding the molecular mechanisms in the progression of aging.