Aging Lung Cells May Provide New Targets for Disease Prevention

Aging raises the risk for nearly every lung disease out there, but researchers from Yale University have found that not all lung cells are to blame.

In a study of lung samples from 60 people aged 11 to 80, researchers found that some lung cells age faster than others.

The investigators used single-cell RNA sequencing and advanced computational methods to identify all cells within each sample, then zeroed in on age-related changes in cell-type proportions, gene expression, and the sequences of genes that reflect changes in DNA acquired since birth, known as somatic mutations.

Two types of lung cells were particularly susceptible to aging: AT2 cells, which produce surfactant, and endothelial cells that line the lung vasculature. These cells exhibited the greatest changes in gene expression and the number of somatic mutations, as well as other age-associated changes.

For example, the team observed decreased expression of genes that drive surfactant production in AT2 cells, which appeared to become more disordered with age.

The authors say their analysis suggests aging is accompanied by an increase in transcriptional entropy across many cell types in the lung, and this increasing disorder in gene regulation may reflect how cells lose their organization and stability as people age.

They also believe this gene expression entropy may be associated with an increase in somatic mutations, which could help scientists pinpoint specific mutations and genetic changes that increase the risk of developing various diseases associated with aging.

This could lead to new treatments aimed at preventing the development of lung diseases.

“While the role of somatic mutations is well known in conditions such as lung cancer, the abundance of such mutations with aging may allow better understanding of the increased predisposition to lung diseases with aging and lead to targeted cell therapies,” said senior study author Naftali Kaminski, MD.

The study was published by Nature Communications. 

Highlighted in RC Buzz March 16, 2026