Age-Stratified Integrative Transcriptomic Analysis Reveals a Conserved Fibrotic Core and Distinct Molecular Signatures in Hypertrophic Cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) exhibits clinical heterogeneity and age-related penetrance, yet its molecular basis across adulthood remains incompletely understood. This study aimed to characterize age-dependent transcriptomic signatures and identify conserved molecular features across adult HCM. Methods: Left ventricular RNA sequencing data from the GSE141910 dataset were analyzed by comparing three age-stratified HCM groups (18–39, 40–59, and ≥60 years) with corresponding age-matched controls. Differentially expressed genes (DEGs) were identified using GEO2R, followed by functional enrichment and protein–protein interaction (PPI) network analysis. Results: A total of 498 DEGs were shared across all age tertiles, while 439, 594, and 353 DEGs were specific to the youngest, middle-aged, and oldest groups, respectively. Shared DEGs exhibited an extracellular matrix (ECM)-related functional profile and formed PPI modules associated with ECM homeostasis and immune regulation. Age-specific analyses revealed enrichment of adaptive immune pathways in younger patients, cell cycle- and interferon-associated processes in the middle-aged group, and ECM remodeling together with senescence-associated processes in older patients. Hub gene analysis further highlighted distinct age-dependent molecular signatures. Conclusions: Our findings suggest that adult HCM is characterized by a conserved fibrotic core accompanied by age-dependent biological programs, providing a framework for future studies investigating age-informed biomarkers and therapeutic targets.