The aging transcriptome and cellular landscape of the human lung in relation to SARS-CoV-2

Ryan D. Chow, Medha Majety and Sidi Chen ()
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Ryan D. Chow: Yale University School of Medicine
Medha Majety: Yale University School of Medicine
Sidi Chen: Yale University School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: Abstract Age is a major risk factor for severe coronavirus disease-2019 (COVID-19). Here, we interrogate the transcriptional features and cellular landscape of the aging human lung. By intersecting these age-associated changes with experimental data on SARS-CoV-2, we identify several factors that may contribute to the heightened severity of COVID-19 in older populations. The aging lung is transcriptionally characterized by increased cell adhesion and stress responses, with reduced mitochondria and cellular replication. Deconvolution analysis reveals that the proportions of alveolar type 2 cells, proliferating basal cells, goblet cells, and proliferating natural killer/T cells decrease with age, whereas alveolar fibroblasts, pericytes, airway smooth muscle cells, endothelial cells and IGSF21+ dendritic cells increase with age. Several age-associated genes directly interact with the SARS-CoV-2 proteome. Age-associated genes are also dysregulated by SARS-CoV-2 infection in vitro and in patients with severe COVID-19. These analyses illuminate avenues for further studies on the relationship between age and COVID-19.

Date: 2021
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DOI: 10.1038/s41467-020-20323-9

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