ScRNA sequencing on human airway epithelium reveals transcriptional changes during healthy aging

Abstract

Aging attenuates the ability of the lung to regenerate lost or damaged tissue and could be responsible for the decline in airway stem cell function. In addition, other naturally occurring aging phenomena such as cellular senescence and epigenetic alterations can impact the progression of many chronic lung diseases (such as COPD and Cancer). Still, how aging affects the human lung on a cellular and molecular level remains unknown. Therefore, it is important to delineate the molecular and cellular changes that occur within the “healthy” aging lung in order to understand and provide a context for the development of lung disease. To elucidate this, we have performed single cell RNA sequencing analysis along with psuedotime analysis on human airway cells from 4 aged healthy non-smoking subjects (65-74 years) and 5 younger healthy non-smoking subjects (20-39 years). The analysis showed that aged basal cells (KRT5+, p63+) expressed significantly higher levels of the AP-1 transcription factor family related genes, as well as an enrichment for genes involved in ROS production and oxidative phosphorylation. Furthermore, the pseudotime analysis identified AGR2 and TFF3, to have an increased expression pattern in ciliated (FOXJ1+) and secretory (SCGB1A1+) aged cells when compared to younger counterparts. In contrast, we found a significant downregulation of genes involved in antigen presentation on the aged ciliated and secretory cells indicating that these cells become less efficient in antigen presentation with age. Taken together, our data reveals that the aging process affects numerous gene and regulatory pathways that need to be further investigated for their involvement in health and disease