There are many serious health conditions and diseases that affect the lungs and are associated with aging, like pneumonia, lung cancer, and chronic obstructive pulmonary disease. Researchers have now found that lung cells seem to age at different rats, and they identified specific types of lung cells that are particularly susceptible to aging. The findings have been reported in Nature Communications, and they could improve therapeutics that are aimed at those cells.
"This data allows us to start thinking about lung aging not as a passive state that we have to accept, but as something that we may be able to modify with therapies and interventions," suggested senior study author Naftali Kaminski, MD, a Professor and Chair at Yale School of Medicine.
In this study, the researchers obtained data characterizing cells from sixty different samples of human lungs. The samples came from donors who ranged from 11 to 80 years old. The data included single-cell RNA sequencing, which identifies genes that are active in a cell at one point in time.
The investigators also determined whether there were changes in the proportions of various types of lung cells, gene activity, or mutations arising in lung cell genomes that occur during a person’s lifetime, so-called somatic mutations.
This effort indicated that lung cells age at different rates. Two types of lung cells showed the most changes in aging rates compared to average cells, which was defined in part using changes in gene expression or increases in somatic mutations. One was found to be a type of cell called AT cells, which generate a surfactant–a molecule that changes surface tension, and helps maintains lung air sac integrity; and the other was lung lining or endothelial cells.
Aging AT2 cells, for example, showed a decrease in the activity of genes related to surfactant production. Patterns of gene expression were also more disordered with increased age.
"Our analysis shows that aging is accompanied by an increase in transcriptional entropy across many cell types in the lung," explained first study author Ruben De Man, an MD-Ph.D. student at Yale School of Medicine. "This rising disorder in gene regulation may be a fundamental feature of how our cells lose their organization and stability as we grow older."
This was accompanied by an increase in somatic mutations, which may reveal specific mutations and genetic changes that raise the risk of different age-related diseases.
"While the role of somatic mutations is well known in conditions such 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," added Kaminski.
Sources: Yale University, Nature Communications
