The lung is a highly complex organ in which a great number of very different cells have to work together to enable normal breathing and protection against infection. If a human lung with all its branches was spread out on the ground, it would cover an area of about 70m². When one then considers that the cells are only a few thousandths of a millimeter in size and are composed of about 40 different, highly specialized cell types, one can begin to understand the complexity involved in investigating processes that affect the entire lung. However, advances in technology have opened up new possibilities in this field for scientists.

"For the current study, we analyzed changes between young and aging lungs down to the single-cell level in a preclinical model," explains study lead. "This was made possible thanks to new single-cell analysis techniques. We were thus able to pinpoint gene activity in the individual lung cells and ascribe it to the changes in the corresponding gene products - i.e. to the proteins," the author explains.* In order to meaningfully collate and interpret all this data, the team relied on AI approaches: "The sheer mass of data is hard for humans to analyze. That's why we develop algorithms to help us to recognize the structure of the data and the biological regulations hidden within it," the author notes.

The study showed that, with increasing age, the genes in the cells no longer behaved in a synchronized manner. "Whereas in younger lungs a particular cell type will control the gen activity very precisely, the gene activity of older lung cells, and thus also their identity, is less constant," the author explains. The scientists are working on the assumption that cells lose epigenetic control during the aging process, which results in different gene activities. Moreover, they demonstrated that certain metabolic pathways in lung cells are altered with increasing age. Authors also observed cell type-specific effects of aging, uncovering increased cholesterol biosynthesis in type-2 pneumocytes and lipofibroblasts and altered relative frequency of airway epithelial cells as hallmarks of lung aging.

But changes also occur outside the cells. Proteomic profiling reveals extracellular matrix remodeling in old mice, including increased collagen IV and XVI and decreased Fraser syndrome complex proteins and collagen XIV. "The structure of the so-called extracellular matrix - in other words, the network of proteins surrounding the cells - changes with age," the author explains. "This can, for example, alter the composition of the structural proteins known as collagens." The scientists now hope to collaborate with their international peers in order to verify the findings of their current study in the human body.

https://www.nature.com/articles/s41467-019-08831-9

http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fan-atlas-of-the-aging&filter=22