| Institution: | 1. Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany;2. Institute for Bioinnovation, Biomedical Sciences Research Center “Alexander Fleming”, Vari, Greece;3. Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany
Clinical Research Unit 5002, University Medical Center Göttingen, Göttingen, Germany;4. Faculty of Biology, Ludwig Maximilians University Munich, Munich, Germany;5. Cluster of Excellence on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany;6. Center for Molecular Medicine Cologne, University and University Hospital of Cologne, Cologne, Germany;7. EIRNA Bio (formerly Ribomaps), Cork, Ireland;8. Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University Medical School, Aachen, Germany;9. Department of NanoBiophotonics, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany |
| Abstract: | Cellular senescence is acknowledged as a key contributor to organismal ageing and late-life disease. Though popular, the study of senescence in vitro can be complicated by the prolonged and asynchronous timing of cells committing to it and by its paracrine effects. To address these issues, we repurposed a small molecule inhibitor, inflachromene (ICM), to induce senescence to human primary cells. Within 6 days of treatment with ICM, senescence hallmarks, including the nuclear eviction of HMGB1 and -B2, are uniformly induced across IMR90 cell populations. By generating and comparing various high throughput datasets from ICM-induced and replicative senescence, we uncovered a high similarity of the two states. Notably though, ICM suppresses the pro-inflammatory secretome associated with senescence, thus alleviating most paracrine effects. In summary, ICM rapidly and synchronously induces a senescent-like phenotype thereby allowing the study of its core regulatory program without confounding heterogeneity. |
