Authors
Towler, A. G., Wang, F., Bi, Y., Bandura, L. J., Zhu, Y., Zhu, J., Perciaccante, A. J., Aballo, T. J., Ji, Q. C., Jin, L., Buck, W., Phillips, L., Kadoya, K., Schnapp, L. M., He, Y., Tian, Y., Ge, Y.
Abstract
The lung extracellular matrix (ECM) governs tissue architecture, mechanics, and function, yet how it remodels with age across sex and anatomical regions remains poorly understood. Here, we performed a systematic multi-factor proteomic analysis of rat lungs to define age-, sex-, and region-dependent remodeling across the tissue landscape. Age emerged as the dominant source of variation, with a conserved aging signature modified by region- and sex-specific effects. Young lungs showed coordinated ECM assembly, balanced proteolysis, and active biosynthetic programs consistent with structural adaptability and mechanical resilience. In contrast, aged lungs exhibited accumulation of mature collagen crosslinks and a more stabilized matrix architecture, indicating progressive matrix maturation and reduced structural plasticity. These changes were accompanied by proteomic signatures of metabolic stress and immune activation, suggesting coordinated remodeling across ECM, metabolic, and immune pathways during lung aging. Aging effects varied across anatomical regions and were more pronounced in females, highlighting context-dependent trajectories within the broader aging program. Age also partially reshaped spatial proteomic heterogeneity across lung compartments. Together, these findings identify matrix stabilization as a central feature of lung aging that links structural remodeling to metabolic-inflammatory imbalance and increased pulmonary vulnerability.
Preprint server:
bioRxiv
The authors list and abstract were imported from bioRxiv on 23 Jun 2026.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 6
- Comments 0