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

Nat Commun. 2021 Jan 4;12(1):4. doi: 10.1038/s41467-020-20323-9.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • A549 Cells
  • Adult
  • Aged
  • Aging / genetics*
  • Aging / metabolism
  • Aging / pathology
  • COVID-19 / genetics*
  • COVID-19 / metabolism
  • COVID-19 / pathology
  • COVID-19 / virology
  • Endothelial Cells / pathology
  • Female
  • Fibroblasts / pathology
  • Gene Expression
  • Humans
  • Lung / metabolism
  • Lung / pathology
  • Lung / physiology*
  • Lung / virology
  • Male
  • Middle Aged
  • Pericytes / pathology
  • RNA-Seq
  • SARS-CoV-2 / isolation & purification
  • Transcriptome
  • Young Adult