Biology subjects

Di Palo, J.

Publications and source records attributed to Di Palo, J..

3 recordsLinked to original sources

bioRxiv2026

Inherent Biomechanical Properties of the Lung: In vivo-Ex vivo Comparisons in Mice

Mammalian lungs operate within a thoracic "cage" composed of parietal pleura, rib cage, skeletal muscle, and diaphragm, yet clinical ventilator metrics largely reflect the combined mechanics of lung and surrounding structures and the thoracic cage. We hypothesized that thoracic boundary conditions selectively alter measured lung biomechanics. We performed paired pulmonary function testing (FlexiVent) in C57BL6 mice of both sexes spanning development through adulthood, measuring quasi-static pressure-volume behavior and dynamic forced-oscillation parameters in vivo (supine, mechanically ventilated) and again ex vivo in the same lungs. In a subset, we additionally compared in vivo and ex vivo {micro}CT-derived lung volumes, including a pressure-fixed ex vivo protocol using snap freezing at controlled inflation pressure. Quasi-static pressure-volume curves were similar between conditions, with near-identity at higher pressures and only modest divergence at low pressures, consistent with thoracic structures primarily modulating recruitment/de-recruitment rather than intrinsic elastic recoil. Maximal volume at 30 cmH2O showed strong in vivo-ex vivo correlation and minimal bias, and static compliance and PV-loop hysteresis exhibited small biases relative to reported disease-model effect sizes. In contrast, dynamic mechanics demonstrated a clear in vivo elevation of tissue damping (G) with only modest change in tissue elastance (H) and little change in Newtonian resistance (Rn), producing a meaningful increase in hysteresivity ( = G/H). This dissociation implicates frequency-dependent mechanical heterogeneity (e.g., time-constant mismatch/pendelluft) imposed or amplified by nonuniform thoracic loading. Ex vivo {micro}CT enabled reliable whole-lung segmentation and correlated with ex vivo PFT volumes at matched pressures, whereas in vivo volumetry showed weaker agreement. These results indicate that thoracic structures contribute modest restriction but disproportionately increase dynamic dissipation and heterogeneity, suggesting that ex vivo functional testing and oscillometry-like metrics may better detect biomechanical changes inherent to lung parenchyma.

physiology↗

bioRxiv2026

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) R{superscript 2} = 0.596, Mean Absolute Error (MAE) = 3.43 months. Adding vascular mechanical parameters (PWV) raised a combined LOO R{superscript 2} 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 R{superscript 2} = 0.960 vs. male-only R{superscript 2} = 0.658). These results establish a multimodal framework for vascular biological age quantification that integrates structural and mechanical aging signatures.

bioengineering↗

bioRxiv2026

Biological Aging of the Cardiopulmonary System

Age-related stiffening of large arteries is a predictor of cardiovascular morbidity and mortality, yet how pulmonary vascular stiffening integrates with right ventricular (RV) and lung functional decline--and how best to quantify "biological" cardiopulmonary aging--remains unclear. Here we map cardiopulmonary aging across the adult murine lifespan by integrating RV, proximal pulmonary artery (PA), and lung biomechanics with single-cell transcriptomics. Using ex vivo biaxial testing of the proximal PA, in vivo echocardiography, and lung mechanics, we find that cardiopulmonary aging is phase-dependent: PA circumferential stiffening and reduced distensibility progress largely linearly with age; whereas, RV remodeling and lung mechanical changes exhibit non-linear trajectories. This is consistent with early intrinsic functional decline of cells and organs followed by later, extrinsic load-dependent structural adaptation. To quantify organ-level biological aging, we apply principal component analysis to PA, RV, and lung feature sets to derive physiology-based aging scores that summarize coordinated variance within and across organs. Anchoring differential gene expression in PA single-cell RNA-seq to these continuous biological aging scores rather than chronological age reveals extensive, cell-type-specific remodeling programs (13,636 genes) that are sparse or non-informative when modeled by chronologic age. Biological aging associates across endothelia, smooth muscle cells, fibroblasts, and perivascular macrophages with increased oxidative phosphorylation signatures alongside suppression of adaptive/regulatory pathways, including impaired endothelial mechanotransduction, reduced smooth muscle Wnt signaling, altered extracellular matrix remodeling programs, and erosion of macrophage innate immune and TGF{beta}/NF-{kappa}B signaling nodes. These findings support a model in which pulmonary arterial stiffening is not merely a marker but an active contributor to cardiopulmonary aging via a biomechanical-metabolic-inflammatory uncoupling that diminishes vasoactive and mechano-adaptive reserve and promotes a positive feedback loop. Together, our work establishes physiology-derived biological aging as a powerful framework for interpreting vascular single-cell aging trajectories and identifies mechanistic pathways to target pulmonary vascular stiffening and preserve cardiopulmonary function with age.

physiology↗