Idiopathic pulmonary fibrosis (IPF) is a progressive, age-associated interstitial lung disease with limited therapeutic options. Current antifibrotics modestly slow the decline but fail to halt or reverse fibrosis. Emerging evidence implicates two central hallmarks of aging-cellular senescence and impaired autophagy-in IPF pathogenesis. Senescent epithelial and stromal cells secrete proinflammatory and profibrotic mediators, while defective autophagic flux exacerbates protein and organelle accumulation, mitochondrial dysfunction, and maladaptive stress responses. Increasingly, these processes are recognized as reciprocally regulated, converging on signaling pathways such as transforming growth factor-β, adenosine monophosphate-activated protein kinase/mechanistic target of rapamycin, nuclear factor kappa-light-chain enhancer of activated B cells, and reactive oxygen species. This review examines the senescence-autophagy axis, outlines conceptual frameworks to reconcile its paradoxical functions, and highlights emerging therapeutic strategies, including drug repurposing and next-generation interventions.
Min et al. (Sun,) studied this question.