Pulmonary Aging: Impact of cell senescence on lung inflammation and repair in endotoxin and Klebsiella pneumoniae induced lung injury
Anatomy and Physiology
Final Report Abstract
The most relevant new findings of our study are: Old mice show a dysregulated activation of the Nlrp3/caspase-1/IL-1β axis in acute lung injury (ALI) that supports the development of neutrophilic pleuritis in old mice compared to young mice upon K. pneumoniae infection. The deregulatory effects were attributable to age-related alterations in the bone marrow rather than the lung, supporting a role for hematopoietic inflamm-aging in lung infections of the elderly. Short chain fatty acids, important metabolites of the gut microbiota, have a beneficial role in the gut-lung axis of the aging organism by reducing pulmonary inflamm-aging and ameliorating enhanced severity of ALI in old mice. The results furthermore emphasized the importance of the gut microbiome and its metabolites in healthy aging beyond the gut. ALI promotes surfactant dysfunction and cellular senescence in alveolar epithelial type II (ATII) cells in old mice. Testing the impact of ATII cell senescence on lung injury and regeneration revealed, however, that ATII cell senescence contributes to and affects regeneration after injury, but is not the main driver of enhanced severity of ALI in old mice.
Publications
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Aging impairs alveolar epithelial type II cell function in acute lung injury. American Journal of Physiology-Lung Cellular and Molecular Physiology, 319(5), L755-L769.
Yazicioglu, Tolga; Mühlfeld, Christian; Autilio, Chiara; Huang, Cheng-Kai; Bär, Christian; Dittrich-Breiholz, Oliver; Thum, Thomas; Pérez-Gil, Jesús; Schmiedl, Andreas & Brandenberger, Christina
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Aging and senescence in alveolar epithelial type II cells affect progenitor cell function and aggravate acute lung injury. 03.03 - Mechanisms of lung injury and repair, 3497. European Respiratory Society.
Brandenberger, C.; Hirsch, M.; Hildebrand, C.; Mühlfeld, C. & Wedekind, D.
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Neutrophilic Pleuritis Is a Severe Complication of Klebsiella pneumoniae Pneumonia in Old Mice. The Journal of Immunology, 209(11), 2172-2180.
Hollwedel, Femke D.; Maus, Regina; Stolper, Jennifer; Jonigk, Danny; Hildebrand, Christina B.; Welte, Tobias; Brandenberger, Christina & Maus, Ulrich A.
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Short-chain fatty acids improve inflamm-aging and acute lung injury in old mice. American Journal of Physiology-Lung Cellular and Molecular Physiology, 324(4), L480-L492.
Hildebrand, Christina B.; Lichatz, Rita; Pich, Andreas; Mühlfeld, Christian; Woltemate, Sabrina; Vital, Marius & Brandenberger, Christina
