Spatial Transcriptomic Analysis Reveals Dysregulated Pro-Inflammatory Signaling in the Aged Lung.

Area of Science:

• Immunology
• Aging Research
• Respiratory Medicine

Background:

• Older individuals face higher risks of respiratory infections due to lung changes and inflammation.
• Mechanisms underlying age-related respiratory vulnerability are not fully understood.
• Rodent models have limitations in translating findings to human respiratory diseases.

Purpose of the Study:

• To investigate age-related differences in lung transcriptional landscapes.
• To identify cellular and molecular mechanisms contributing to increased respiratory infection susceptibility in older individuals.
• To utilize rhesus macaques as a translational model for human lung aging.

Main Methods:

• Visium spatial transcriptomics was employed to analyze lung tissue from young and aged rhesus macaques.
• Gene expression patterns were compared between age groups to identify differential cellular responses.
• Immune and structural cell clusters were identified and characterized.

Main Results:

• Aged lungs exhibited a pro-inflammatory transcriptional bias compared to a regulatory phenotype in young lungs.
• Key cellular signaling pathways for adhesion and tissue maintenance were reduced in aged lungs.
• Significant differences in immune cell populations and gene expression were observed between young and aged macaques.

Conclusions:

• Aged lungs are predisposed to hyperinflammatory responses, potentially leading to increased immune-mediated damage.
• These findings highlight age-related immune dysregulation in the lung.
• Rhesus macaques offer a valuable model for studying human lung aging and disease.