ScRNA sequencing on human airway epithelium reveals metabolic 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 to understand and provide a context for the development and progression of lung disease. To elucidate this, we have performed single cell and pseudobulk RNA sequencing analysis along with pseudotime 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 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, pseudobulk analysis identified fatty acid metabolism related genes such as FABP4 and APOE to have an increased expression pattern young cells when compared to aged counterparts. Taken together, our data reveals that the aging process affects numerous gene and regulatory pathways, most interestingly the metabolic pathways. We hope that these pathways can be further investigated and targeted for their involvement in health and disease.