Single-cell atlas of human lung aging identifies cell type dyssynchrony and increased transcriptional entropy

Age is a major risk factor for lung disease. We characterized the changing cellular, transcriptional, and genomic landscape of human lung aging using single-cell RNA sequencing. We find that lung aging is cell-type dyssynchronous, with alveolar epithelial and endothelial cells exhibiting the greatest transcriptional changes. Among alveolar epithelial cells, aging is associated with a decreased relative proportion of surfactant-expressing SPChigh AT2 cells. Among alveolar capillary cells, we observed loss of differentiation and capillary function. Analysis of somatic mutations called from single-cell data revealed an increase with aging, with alveolar epithelial and endothelial cell types exhibiting greater…

• UD
  U.S. Department of Veterans Affairs
• YU
  Yale University

  Award: P30AG021342
• NI
  National Institutes of Health

  Awards: R01HL141852, U01HL145567, T32GM086287, T32GM136651, P30AG021342, UH2HL123886, R01HL127349
• NI
  National Institute on Aging

  Awards: R03AG074063, P30AG021342
• NH
  National Heart, Lung, and Blood Institute

  Awards: UH2HL123886, R01HL141852, U01HL145567, P30AG021342, R01HL127349
• NI
  National Institute of General Medical Sciences

  Awards: T32GM136651, T32GM086287