한빛사논문
- 조회935
Seoyeon Lee1,8, Mohammad Naimul Islam2,8, Kaveh Boostanpour1, Dvir Aran3, Guangchun Jin2, Stephanie Christenson1, Michael A. Matthay1, Walter L. Eckalbar1, Daryle J. DePianto4, Joseph R. Arron4, Liam Magee1, Sunita Bhattacharya2,5, Rei Matsumoto6, Masaru Kubota6, Donna L. Farber6,7, Jahar Bhattacharya2,8,*, Paul J. Wolters1,8,* & Mallar Bhattacharya1,8,*
1Department of Medicine, Division of Pulmonary, Critical Care, Allergy, and Sleep, University of California, San Francisco, CA, USA. 2Lung Biology Laboratory, Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Vagelos College of Physicians and Surgeons of Columbia University, New York, NY, USA. 3Lorry I. Lokey Interdisciplinary Center for Life Sciences & Engineering, Technion Israel Institute of Technology, Haifa, Israel. 4Genentech Research and Early Development, Genentech, Inc., South San Francisco, CA, USA. 5Department of Pediatrics, Vagelos College of Physicians and Surgeons of Columbia University, New York, NY, USA. 6Department of Surgery, Vagelos College of Physicians and Surgeons of Columbia University, New York, NY, USA. 7Department of Microbiology and Immunology, Columbia University, New York, NY, USA. 8These authors contributed equally: Seoyeon Lee, Mohammad Naimul Islam; Jahar Bhattacharya, Paul J. Wolters, and Mallar Bhattacharya.
*Corresponding author.
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.
논문정보
- Research article
- 2021년 11월 (BRIC 등록일 2021-11-05)
- 국외 연구진
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