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

Nicholas S. Rhoades, Michael Davies, Sloan A. Lewis, Isaac R. Cinco, Steven G. Kohama, Luiz E. Bermudez, Kevin L. Winthrop, Cristina Fuss, Julie A. Mattison, Eliot R. Spindel, Ilhem Messaoudi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number110725
JournalCell Reports
Volume39
Issue number3
DOIs
StatePublished - Apr 19 2022
Externally publishedYes

Keywords

  • BAL
  • CP: Immunology
  • aging
  • lung
  • lung immunology
  • microbiome
  • pulmonary function
  • rhesus macaque

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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