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Molecular programs of fibrotic change in aging human lung

Author

Listed:
  • 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
    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
    Columbia University)

  • Jahar Bhattacharya

    (Vagelos College of Physicians and Surgeons of Columbia University)

  • Paul J. Wolters

    (University of California)

  • Mallar Bhattacharya

    (University of California)

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.

Suggested Citation

  • 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 Mage, 2021. "Molecular programs of fibrotic change in aging human lung," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26603-2
    DOI: 10.1038/s41467-021-26603-2
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    References listed on IDEAS

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