The aging transcriptome and cellular landscape of the human lung in relation to SARS-CoV-2.
Ryan D ChowMedha MajetySidi ChenPublished in: Nature communications (2021)
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.
Keyphrases
- sars cov
- coronavirus disease
- respiratory syndrome coronavirus
- induced apoptosis
- cell cycle arrest
- dendritic cells
- cell death
- gene expression
- cell adhesion
- transcription factor
- signaling pathway
- machine learning
- oxidative stress
- rna seq
- community dwelling
- big data
- dna methylation
- endoplasmic reticulum stress
- bioinformatics analysis
- middle aged