Severe obesity causes lungs to age prematurely, study suggests

Credit: Cell Reports (2025). DOI: 10.1016/j.celrep.2025.116285

A research team has determined that severe obesity causes the lungs to age faster. The team was led by Prof. Dr. Veronika Lukacs-Kornek from the “ImmunoSensation2” Cluster of Excellence at the University of Bonn and the Institute for Molecular Medicine and Experimental Immunology (IMMEI) at the University Hospital Bonn (UKB). The findings have been published in Cell Reports.

The study investigates how the lungs adapt to nutritional challenges in obesity. The research team shows that obesity remodels the extracellular matrix in the lungs—the protein-based “scaffolding” that gives the lungs their shape and stability. These changes in lung tissue are similar to those that normally occur with age and suggest that being overweight causes the lungs to “age” prematurely.

The team used state-of-the-art multi-omics approaches to simultaneously examine proteins, fats and genes for specific questions. They combined this analysis with microscopic image analyses and experiments that show how the lungs actually work. The researchers compared the lungs of obese and lean mice, analyzed human connective tissue cells in the lungs, and took a close look at the composition of the lungs—enabling them to understand both molecular and functional changes.

In obesity, lung fibroblasts, i.e., connective tissue cells, specifically accumulate fat, become more mobile and show early signs of premature aging. At the same time, the matrisome, the “scaffolding” of the lung, changes and the balance of certain protease inhibitors is disrupted. These changes make the lungs less elastic, which could explain why obesity is often associated with breathing difficulties. Interestingly, these changes are similar to those normally seen in older people—pointing to obesity as a driver of accelerated lung aging.

One of the biggest challenges was developing methods to analyze the complex connective tissue of the lungs—the so-called fibroblastic stroma—which consists of many different cell types. In addition, the extracellular matrix is also difficult to study because many of its proteins are insoluble and have a very complex structure.