Rapid and synchronous chemical induction of replicative-like senescence via a small molecule inhibitor
© 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
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| Enthalten in: |
Aging cell - 23(2024), 4 vom: 19. Apr., Seite e14083 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Palikyras, Spiros [VerfasserIn] |
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| Links: |
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| Themen: |
3D genome organization |
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| Anmerkungen: |
Date Completed 17.04.2024 Date Revised 25.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/acel.14083 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a 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 | ||
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| 700 | 1 | |a Stavropoulou, Athanasia |e verfasserin |4 aut | |
| 700 | 1 | |a Danieli-Mackay, Adi |e verfasserin |4 aut | |
| 700 | 1 | |a Varamogianni-Mamatsi, Vassiliki |e verfasserin |4 aut | |
| 700 | 1 | |a Hörl, David |e verfasserin |4 aut | |
| 700 | 1 | |a Nasiscionyte, Simona |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Yajie |e verfasserin |4 aut | |
| 700 | 1 | |a Papadionysiou, Ioanna |e verfasserin |4 aut | |
| 700 | 1 | |a Papadakis, Antonis |e verfasserin |4 aut | |
| 700 | 1 | |a Josipovic, Natasa |e verfasserin |4 aut | |
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| 700 | 1 | |a O'Connell, Aoife |e verfasserin |4 aut | |
| 700 | 1 | |a Loughran, Gary |e verfasserin |4 aut | |
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| 700 | 1 | |a Wagner, Wolfgang |e verfasserin |4 aut | |
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