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In this fibrotic microenvironment, senescence\u2010associated \u03b2\u2010galactosidase (SA\u2010\u03b2\u2010Gal) serves as a key biomarker. However, existing SA\u2010\u03b2\u2010Gal molecular probes suffer from signal diffusion and rapid clearance due to the extracellular leakage, compromising imaging fidelity. To address this issue, an enzyme\u2010activated covalent labelling strategy is proposed, and as a design paradigm developing\n                    <jats:bold>TCFM\u2010Gal<\/jats:bold>\n                    , a imaging tool integrating \u03b2\u2010galactosidic fluorophore with an ortho\u2010difluoromethyl leaving group. Upon SA\u2010\u03b2\u2010Gal\u2010mediated hydrolysis,\n                    <jats:bold>TCFM\u2010Gal<\/jats:bold>\n                    generates a quinone methide intermediate that covalently anchors to surrounding nucleophiles, confining fluorescence within lysosomes. In senescent cells,\n                    <jats:bold>TCFM\u2010Gal<\/jats:bold>\n                    achieves extended lysosome\u2010retained imaging, maintaining over 85% signal retention within 24\u00a0h. In the IPF model,\n                    <jats:bold>TCFM\u2010Gal<\/jats:bold>\n                    enables longitudinal tracking of senescent cells and maintains a high signal intensity after 24\u00a0h. Rapid circulatory washout and high interstitial fluid pressure make conventional probes ineffective in the lungs.\n                    <jats:bold>TCFM\u2010Gal<\/jats:bold>\n                    overcomes this not just by sensing, but by anchoring the signals in situ. Moreover,\n                    <jats:bold>TCFM\u2010Gal<\/jats:bold>\n                    facilitates staging assessments of fibrosis progression by quantifying the senescence burden across disease phases. This study establishes an enzyme\u2010activated covalent labeling paradigm for high\u2010fidelity senescence imaging, advancing the spatiotemporal mapping of senescence in lung diseases.\n                  <\/jats:p>","DOI":"10.1002\/smll.75215","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T06:10:44Z","timestamp":1786515044000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Covalent Anchoring of Enzyme\u2010Activatable Fluorescent Signals for in Situ Imaging and Longitudinal Staging of Cellular Senescence in Pulmonary Fibrosis"],"prefix":"10.1002","volume":"22","author":[{"given":"Feiyi","family":"Chu","sequence":"first","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences Central South University Changsha 410013 People's Republic of 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