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

doi:10.1016/j.celrep.2022.110725

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 journal › Article › peer-review

14 Scopus citations

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 language	English
Article number	110725
Journal	Cell Reports
Volume	39
Issue number	3
DOIs	https://doi.org/10.1016/j.celrep.2022.110725
State	Published - Apr 19 2022

Bibliographical note

Publisher Copyright:
© 2022 The Authors

Funding

This work was supported, in part, by the intramural program of the National Institute on Aging, NIH (R01AI152258-02). NSR was supported by an NIH training grant (T32AI007319-32). The authors thank the ONPRC Division of Comparative Medicine and veterinary staff for their expert animal care. The authors also thank the veterinary technicians at the NIA nonhuman primate core for sample collection and support from the Division of Veterinary Resources animal care team (P51-OD011092). The graphical abstract was generated using graphics from BioRender.com. N.S.R. S.G.K. E.R.S, L.E.B. K.L.P. and I.M. conceived and designed the experiments. M.D. S.G.K. J.A.M. and E.R.S. identified suitable animals and collected samples. N.S.R. M.D. S.A.L. and I.R.C. performed the experiments. N.S.R, M.D. S.A.L. and C.F. analyzed the data. N.S.R. E.R.S. and I.M. interpreted the results and wrote the paper. All authors have read and approved the final draft of the manuscript. The authors declare no competing interests. This work was supported, in part, by the intramural program of the National Institute on Aging, NIH ( R01AI152258-02 ). NSR was supported by an NIH training grant ( T32AI007319-32 ). The authors thank the ONPRC Division of Comparative Medicine and veterinary staff for their expert animal care. The authors also thank the veterinary technicians at the NIA nonhuman primate core for sample collection and support from the Division of Veterinary Resources animal care team ( P51-OD011092 ). The graphical abstract was generated using graphics from BioRender.com .

Funders	Funder number
Division of Veterinary Resources animal care team	P51-OD011092
ONPRC Division of Comparative Medicine
National Institutes of Health (NIH)	T32AI007319-32
National Institute on Aging
National Institute of Allergy and Infectious Diseases	R01AI152258

Keywords

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

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2022.110725

Cite this

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

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{\textquoteright} functional, microbial, and immunological landscape that explain increased prevalence and severity of respiratory diseases in the elderly.",

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AU - Kohama, Steven G.

AU - Bermudez, Luiz E.

AU - Winthrop, Kevin L.

AU - Fuss, Cristina

AU - Mattison, Julie A.

AU - Spindel, Eliot R.

AU - Messaoudi, Ilhem

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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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