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.
【저자키워드】 viral infection, Data integration, Immunogenetics, 【초록키워드】 COVID-19, coronavirus disease, Transcriptome, SARS-CoV-2, Mitochondria, coronavirus, severe COVID-19, Stress, SARS-COV-2 infection, lung, in vitro, airway smooth muscle, risk factor, dendritic cells, Replication, cells, severity of COVID-19, endothelial cells, human lung, Patient, age, pericytes, proteome, change, dendritic cell, Endothelial cell, cellular, Analysis, fibroblasts, the strongest, stress responses, smooth muscle, transcriptomes, goblet cells, basal cells, Older, Factor, severe coronavirus disease, SARS-CoV-2 infection in vitro, proportions, SARS-CoV-2 proteome, deconvolution analysis, alveolar, IGSF21, responses, populations, feature, Cell, decrease, transcriptional, identify, proportion, reduced, characterized, contribute, analysis, reveal, dysregulated, the SARS-CoV-2, transcriptionally, 【제목키워드】 Transcriptome, SARS-CoV-2, human lung, cellular,