Study Maps Biological Aging of Heart and Lung System, Identifies Key Molecular Mechanisms
Researchers mapped cardiopulmonary aging across the adult mouse lifespan by integrating biomechanical measurements of the pulmonary artery, right ventricle, and lungs with single-cell gene expression data. They found that aging in this system is phase-dependent: pulmonary artery stiffening progresses largely linearly, while right ventricular remodeling and lung mechanical changes follow non-linear trajectories. The work establishes a physiology-based biological aging framework that outperforms chronological age in identifying cell-type-specific molecular remodeling programs, potentially pointing to new therapeutic targets.
A new preprint study used a multi-modal approach—combining ex vivo biomechanical testing, in vivo echocardiography, lung mechanics measurements, and single-cell RNA sequencing—to characterize how the cardiopulmonary system ages in mice across the full adult lifespan. The researchers found that pulmonary artery circumferential stiffening and reduced distensibility increase largely linearly with age, while right ventricular remodeling and lung mechanical changes follow non-linear trajectories, suggesting an early phase of intrinsic cellular decline followed by later structural adaptation driven by external mechanical loads. To quantify biological rather than chronological aging, the team applied principal component analysis to biomechanical data from the pulmonary artery, right ventricle, and lungs, generating organ-level 'aging scores.' Anchoring differential gene expression analysis to these biological aging scores rather than to chronological age revealed 13,636 age-associated genes across cell types—a far richer dataset than chronological age alone provided. Key molecular signatures included increased oxidative phosphorylation, impaired endothelial mechanotransduction, reduced smooth muscle Wnt signaling, altered extracellular matrix remodeling, and erosion of macrophage immune signaling nodes involving TGF-β and NF-κB. The authors propose that pulmonary arterial stiffening is not merely a passive marker of aging but an active contributor to cardiopulmonary decline through a biomechanical-metabolic-inflammatory feedback loop that erodes vasoactive and mechano-adaptive reserve over time.
What's missing
As a preprint posted on bioRxiv, this study has not yet undergone formal peer review, and its findings should be interpreted with that caveat. The study is conducted entirely in mice, and it is unclear how well the phase-dependent aging trajectories and specific molecular pathways identified will translate to human cardiopulmonary aging. The biological aging scores derived here are organ- and species-specific constructs whose external validity in human cohorts or other disease contexts has not been tested. The study does not address whether interventions targeting the identified pathways (e.g., Wnt signaling, oxidative phosphorylation) can slow or reverse cardiopulmonary aging in vivo.
What different sources said
- bioRxivCenter
Biological Aging of the Cardiopulmonary System
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