Longevity & AgingSENP1-Sirt3 Axis Shields Lung Stem Cells from Oxidative Damage and Fibrosis
Researchers identified that the SENP1-Sirt3 signaling axis is suppressed in alveolar type II (AT2) stem cells during bleomycin-induced lung injury. By engineering mice with a Sirt3 SUMOylation-resistant mutation (K223R), the team showed that activating this axis reduces mitochondrial ROS production, decreases AT2 cell apoptosis, and boosts AT2 proliferation and differentiation into healthy type I cells. The intervention also curtailed the emergence of pro-fibrotic KRT8+ transitional cells, reduced inflammatory cytokines, and diminished collagen deposition. Transcriptomic analysis revealed enhanced Wnt signaling and lipid metabolism pathways underlying these benefits. Antioxidant N-acetylcysteine recapitulated similar protective effects, reinforcing ROS clearance as the core mechanism.
