Authors
Spiros Palikyras, Konstantinos Sofiadis, Athanasia Stavropoulou, Adi Danieli‐Mackay, Vassiliki Varamogianni‐Mamatsi, David Hörl, Simona Nasiscionyte, Yajie Zhu, Ioanna Papadionysiou, Antonis Papadakis, Natasa Josipovic, Anne Zirkel, Aoife O'Connell, Gary Loughran, James Keane, Audrey Michel, Wolfgang Wagner, Andreas Beyer, Hartmann Harz, Heinrich Leonhardt, Grazvydas Lukinavicius, Christoforos Nikolaou, Argyris Papantonis
Publication date
2024/4
Journal
Aging Cell
Volume
23
Issue
4
Pages
e14083
Description
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 …