期刊
NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-020-20323-9
关键词
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资金
- NIH Medical Scientist Training Program Training Grant [T32GM007205]
- NIH/NCI [F30CA250249]
- NIH/NCI/NIDA [DP2CA238295, 1R01CA231112, U54CA209992-8697, R33CA225498, RF1DA048811]
- Do.D. [W81XWH-20-1-0072, PR201784]
- Chen Lab discretionary funds
Age is a major risk factor for severe illness from COVID-19, and the heightened severity of COVID-19 in older populations may be related to age-associated changes in the transcriptome and cellular landscape of the aging lung. Specific age-associated cells and genes interact with the SARS-CoV-2 proteome and are dysregulated by SARS-CoV-2 infection in vitro and in patients with severe COVID-19.
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. Age is one of the strongest risk factors for severe illness from COVID-19. By integrating human lung transcriptomes with experimental data on SARS-CoV-2, the authors pinpoint specific age-associated factors that could contribute to the heightened severity of COVID-19 in older populations.
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