Umami induces pulmonary epithelial senescence via L-glutamic acid-triggered minority MOMP

Although cellular senescence in pulmonary epithelial cells is a recognized driver of chronic lung diseases, the role of dietary factors in initiating this process remains poorly defined. Here, we identify monosodium glutamate (MSG), the primary source of umami taste, as a trigger of a novel dietary-lung axis. We demonstrate that chronic intake of high amounts of MSG elevates pulmonary L-glutamic acid (Glu) levels, which activate an NMDAR-miMOMP signaling cascade in pulmonary epithelial cells, leading to cellular senescence and lung injury. This mechanism is consistent across multiple high-Glu diets, including high-fat and high-protein regimens. Furthermore, we demonstrate that high-Glu diets exacerbate pulmonary fibrosis progression by increasing the senescence burden. Our findings suggest that dietary Glu is a modifiable risk factor for chronic lung diseases and reveal that the NMDAR-miMOMP-senescence axis is a potential therapeutic target for metabolic respiratory syndromes.