Molecular programs of fibrotic change in aging human lung

Seoyeon Lee, Mohammad Naimul Islam, Kaveh Boostanpour, Dvir Aran, Guangchun Jin, Stephanie Christenson, Michael A. Matthay, Walter L. Eckalbar, Daryle J. DePianto, Joseph R. Arron, Liam Magee, Sunita Bhattacharya, Rei Matsumoto, Masaru Kubota, Donna L. Farber, Jahar Bhattacharya (), Paul J. Wolters () and Mallar Bhattacharya ()
Additional contact information
Seoyeon Lee: University of California
Mohammad Naimul Islam: Vagelos College of Physicians and Surgeons of Columbia University
Kaveh Boostanpour: University of California
Dvir Aran: Technion Israel Institute of Technology
Guangchun Jin: Vagelos College of Physicians and Surgeons of Columbia University
Stephanie Christenson: University of California
Michael A. Matthay: University of California
Walter L. Eckalbar: University of California
Daryle J. DePianto: Genentech, Inc.
Joseph R. Arron: Genentech, Inc.
Liam Magee: University of California
Sunita Bhattacharya: Vagelos College of Physicians and Surgeons of Columbia University
Rei Matsumoto: Vagelos College of Physicians and Surgeons of Columbia University
Masaru Kubota: Vagelos College of Physicians and Surgeons of Columbia University
Donna L. Farber: Vagelos College of Physicians and Surgeons of Columbia University
Jahar Bhattacharya: Vagelos College of Physicians and Surgeons of Columbia University
Paul J. Wolters: University of California
Mallar Bhattacharya: University of California

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: Abstract Lung fibrosis is increasingly detected with aging and has been associated with poor outcomes in acute lung injury or infection. However, the molecular programs driving this pro-fibrotic evolution are unclear. Here we profile distal lung samples from healthy human donors across the lifespan. Gene expression profiling by bulk RNAseq reveals both increasing cellular senescence and pro-fibrotic pathway activation with age. Quantitation of telomere length shows progressive shortening with age, which is associated with DNA damage foci and cellular senescence. Cell type deconvolution analysis of the RNAseq data indicates a progressive loss of lung epithelial cells and an increasing proportion of fibroblasts with age. Consistent with this pro-fibrotic profile, second harmonic imaging of aged lungs demonstrates increased density of interstitial collagen as well as decreased alveolar expansion and surfactant secretion. In this work, we reveal the transcriptional and structural features of fibrosis and associated functional impairment in normal lung aging.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26603-2

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DOI: 10.1038/s41467-021-26603-2

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