Transcriptomic Insights into the Association of IL-1 Signaling with the Senescence-Associated Secretory Phenotype in...

Cellular senescence is a stable growth-arrested state accompanied by the senescence-associated secretory phenotype (SASP), a complex inflammatory secretome that contributes to tissue remodeling, chronic inflammation, and age-related disease. Although multiple signaling pathways have been implicated in SASP regulation, the extent to which interleukin-1 (IL-1) signaling is associated with the organization of SASP-associated transcriptional programs remains incompletely defined at the transcriptomic level.

Here, we performed a focused in silico analysis of a publicly available RNA-sequencing dataset (GSE63577) profiling primary human fibroblasts undergoing replicative senescence. Differential expression analysis revealed broad inflammatory remodeling in senescent fibroblasts, including robust upregulation of canonical SASP-associated cytokines, chemokines, and matrix-related factors. Targeted visualization using a curated, literature-defined SASP gene panel confirmed consistent transcriptional activation of key SASP components during replicative senescence.

To assess transcriptional associations, we performed correlation-based network analysis centered on IL1A and IL1B. This analysis demonstrated strong transcriptional coupling between IL-1 signaling components, NF-κB-related genes, and SASP-associated transcripts, revealing a highly connected inflammatory module embedded within the senescence transcriptome. Pathway-level integration using curated gene sets further highlighted IL-1 signaling, cytokine signaling, and NF-κB-related pathways as dominant features of senescence-associated transcriptional changes. These patterns were further supported by analysis of an independent fibroblast senescence dataset (GSE41714), demonstrating consistent IL-1-associated and SASP-related transcriptional trends across experimental systems.

Together, these findings suggest that IL-1 signaling is consistently associated with a central position within the SASP-associated transcriptional network during replicative senescence in human fibroblasts. Therefore, the present study contributes transcriptomic network-level evidence supporting an association between IL-1 signaling and coordinated SASP-associated inflammatory programs, and highlights its potential relevance for intervention strategies.