Functional, transcriptional, and microbial shifts associated with healthy pulmonary aging in rhesus macaques

Highlights

• Rhesus macaques display the functional hallmarks of healthy pulmonary aging

• Aging increases frequency of myeloid cells at the expense of T cells in the lungs

• Aging shifts from GRZMB⁺ to IFNG⁺ CD8⁺ T cells and fewer IL1B⁺ lung macrophages

• Tropheryma spp. is highly prevalent in the rhesus macaque lung microbiome

Summary

Older individuals are at increased risk of developing severe respiratory infections. However, our understanding of the impact of aging on the respiratory tract remains limited as samples from healthy humans are challenging to obtain and results can be confounded by variables such as smoking and diet. Here, we carry out a comprehensive cross-sectional study (n = 34 adult, n = 49 aged) to define the consequences of aging on the lung using the rhesus macaque model. Pulmonary function testing establishes similar age and sex differences as humans. Additionally, we report increased abundance of alveolar and infiltrating macrophages and a concomitant decrease in T cells were in aged animals. scRNAseq reveals shifts from GRZMB to IFN expressing CD8⁺ T cells in the lungs. These data provide insight into age-related changes in the lungs’ functional, microbial, and immunological landscape that explain increased prevalence and severity of respiratory diseases in the elderly.