Abstract
This study investigates the complex relationship between cellular senescence, aging, and pulmonary fibrosis through a comprehensive analysis of bulk RNA-seq data from patients with idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), and scleroderma. Using differential expression (DE) and age-associated differential expression (AADE) analyses, we revealed a paradoxical pattern: senescence-related gene sets were significantly downregulated in disease comparisons but progressively upregulated with aging within these same diseases. Gene set enrichment analysis (GSEA) revealed that gene sets associated with DNA damage/telomere stress and oxidative stress were among the most enriched senescence inducers in fibrotic disease states, while cellular senescence and SASP pathways appeared increasingly enriched with age. Through latent factor analysis using SLIDE, we identified four significant factors strongly associated with senescence pathways across different disease conditions. These latent factors showed significant enrichment for histone genes, which were consistently downregulated in disease conditions independent of age, suggesting a possible role for chromatin remodeling in senescence-driven fibrosis. These results provide insights into the mechanistic links between senescence and fibrotic lung diseases, highlighting potential targets for therapeutic intervention while emphasizing the importance of considering both disease context and aging when interpreting senescence-related transcriptional signatures in pulmonary fibrosis.
Library of Congress Subject Headings
Pulmonary fibrosis; Cells--Aging; Gene expression
Publication Date
5-2025
Document Type
Thesis
Student Type
Graduate
Degree Name
Bioinformatics (MS)
College
College of Science
Advisor
Jishnu Das
Advisor/Committee Member
Gregory Babbitt
Advisor/Committee Member
Bolaji Thomas
Recommended Citation
Lee, Crystal, "Investigating the Relationship Between Cellular Senescence and Pulmonary Fibrosis" (2025). Thesis. Rochester Institute of Technology. Accessed from
https://repository.rit.edu/theses/12097
Campus
RIT – Main Campus
Plan Codes
BIOINFO-MS