Disease pathogenicity in Hutchinson-Gilford progeria syndrome mice: insights from lung-associated alterations.

backgroundHutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by accelerated aging, impaired growth, disrupted lipid metabolism, and reduced lifespan.

methodsPrior research has primarily focused on cardiovascular manifestations, our research sheds light on multiple organs that underwent significant age-related changes validated by tissue cross-sections H&E, Masson's trichrome, and β-galactosidase staining.

resultsAmong these pathologies tissues, the lung was severely affected and substantiated by clinical data of pulmonary anomalies from our HGPS patients. Biochemical and histological analyses of lung tissue from the HGPS mouse model revealed elevated Progerin expression, abnormal NAD metabolism, cellular senescence markers (higher level of p16 and p27, lower level of ki67), and various age-related morphology changes, including fibrosis, inflammation, and thickening of alveolar walls. Transcriptomic analyses of lung tissue indicated that down-regulated genes (Thy1, Tnc, Cspg4, Ccr1) were associated with extracellular space, immune response, calcium signaling pathway, osteoclast differentiation, and lipid binding pathway.

conclusionsThis study unveiled the previously overlooked organs involved in HGPS pathogenesis and suggested a specific emphasis on the lung. Our findings suggest that pulmonary abnormalities may contribute to disease progression, warranting further investigation into their role in HGPS monitoring and management.