Paper Title
TRANSCRIPTOMIC PROFILING REVEALS SUSTAINED INFLAMMATORY SIGNATURES IN AGED LUNGS POST-IAV INFECTION

Abstract
Aging significantly alters host immune responses to respiratory viral infections such as influenza A virus (IAV), but the molecular basis of these differences remains incompletely understood. In this study, we performed comprehensive cytokine expression profiling using bulk RNA-sequencing data from dataset GSE202324, comprising lung tissue from young (16-week-old) and aged (80-week-old) mice at multiple time points following IAV infection. Differential expression analysis revealed a pronounced upregulation of pro-inflammatory cytokines, including Il1b, TNF, and Cxcl10, particularly at Day 9 post-infection, with aged mice exhibiting a more sustained inflammatory response compared to their younger counterparts. Time-course comparisons (Day 3 vs. Day 9) identified persistent activation of interferon-stimulated genes and chemokines, indicating delayed resolution of inflammation in aged lungs. Functional enrichment and pathway analysis using Reactome and KEGG databases highlighted the upregulation of innate immune pathways such as interferon signaling, cytokine–cytokine receptor interaction, and NF-κB activation. Hierarchical clustering of cytokine genes further delineated age- and time-specific patterns of immune dysregulation. Together, these findings underscore the role of age-associated immune remodeling in shaping the trajectory of pulmonary antiviral responses and identify candidate cytokines and pathways that may inform future therapeutic strategies for elderly populations at heightened risk of severe influenza outcomes. Keywords - Influenza A Virus. Cytokine Profiling, Aging, RNA-Seq, Lung Immune Response