Biological Aging of the Cardiopulmonary System

Area of Science:

• Cardiopulmonary Aging Research
• Vascular Biomechanics
• Single-Cell Transcriptomics

Background:

• Age-related stiffening of large arteries predicts cardiovascular disease.
• The integration of pulmonary vascular stiffening with right ventricular (RV) and lung decline is not well understood.
• Quantifying biological cardiopulmonary aging requires further investigation.

Purpose of the Study:

• To map cardiopulmonary aging across the adult murine lifespan.
• To integrate RV, pulmonary artery (PA), and lung biomechanics with single-cell transcriptomics.
• To develop physiology-based biological aging scores for organ-level aging assessment.

Main Methods:

• Ex vivo biaxial testing of the proximal PA, in vivo echocardiography, and lung mechanics.
• Principal component analysis applied to PA, RV, and lung feature sets to derive aging scores.
• Anchoring differential gene expression from PA single-cell RNA-seq to biological aging scores.

Main Results:

• Cardiopulmonary aging is phase-dependent: PA stiffening is linear, while RV and lung changes are non-linear.
• Biological aging scores revealed extensive, cell-type-specific remodeling programs (13,636 genes) not apparent with chronological age.
• Aging associates with increased oxidative phosphorylation and suppressed adaptive pathways, including impaired mechanotransduction and signaling.

Conclusions:

• Pulmonary arterial stiffening actively contributes to cardiopulmonary aging through biomechanical-metabolic-inflammatory uncoupling.
• Physiology-derived biological aging provides a framework for interpreting vascular aging and identifying therapeutic targets.
• Targeting pulmonary vascular stiffening may preserve cardiopulmonary function with age.