Effect of aging on pulmonary cellular responses during mechanical ventilation.

Summary

In ventilated mice, aging amplified surfactant dysfunction and microvascular leak but attenuated inflammatory signaling. Single-cell RNA-Seq revealed blunted macrophage responses and altered endothelial junction programs, with in vitro assays confirming impaired endothelial barrier in aged cells.

Key Findings

• Aging increased surfactant dysfunction and microvascular permeability during mechanical ventilation.
• Inflammatory responses were attenuated in aged lungs, with blunted alveolar macrophage activation.
• Aged endothelial cells showed altered cell-cell junction programs and impaired barrier formation in vitro.

Clinical Implications

Elderly patients may require stricter lung-protective ventilation (lower driving pressure and tidal strain) and fluid-conservative strategies; endothelial-protective interventions merit testing.

Limitations

• Preclinical murine study with male mice limits generalizability to human, female, and diverse clinical populations
• Short-term injury assessment without long-term outcome evaluation

Future Directions

Test endothelial-targeted and surfactant-stabilizing strategies in aged models; validate single-cell signatures and barrier phenotypes in human ARDS cohorts.