Microstructural and Biomechanical Determinants of Biological Aging

The pulmonary artery undergoes measurable structural and mechanical deterioration with age, but whether these changes can be integrated into a quantitative normative aging prediction model has not been demonstrated. Using two-photon imaging and paired vascular mechanical measurements from C57BL6 mice spanning 6 to 24 months, we developed a multimodal support vector regression (SVR) model integrating collagen fiber orientation, straightness, and hemodynamic mechanical parameters to predict normative age. Fiber orientation was encoded via the von Mises probability density function referenced to the circumferential and axial vessel wall axes providing a principled circular-variable encoding of both mean direction and concentration. The microstructure-only model achieved leave-one-out (LOO) R² = 0.596, Mean Absolute Error (MAE) = 3.43 months. Adding vascular mechanical parameters (PWV) raised a combined LOO R² to 0.834 (MAE = 2.26 months), a 40.1% improvement. Because pulmonary vascular and parenchymal aging are mechanistically coupled, lung mechanics were included as a complementary readout to assess whether airway mechanics contribute independent predictive signal beyond vascular microstructure alone. A sex dimorphism was observed, where females drove the majority of the collagen-based predictive signal (female-only R² = 0.960 vs. male-only R² = 0.658). These results establish a multimodal framework for vascular biological age quantification that integrates structural and mechanical aging signatures.