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Rapid and synchronous chemical induction of replicative-like senescence via a small molecule inhibitor
Aging Cell ( IF 8.0 ) Pub Date : 2024-01-09 , DOI: 10.1111/acel.14083 Spiros Palikyras 1 , Konstantinos Sofiadis 1 , Athanasia Stavropoulou 2 , Adi Danieli-Mackay 1, 3 , Vassiliki Varamogianni-Mamatsi 1 , David Hörl 4 , Simona Nasiscionyte 4 , Yajie Zhu 1 , Ioanna Papadionysiou 1 , Antonis Papadakis 5 , Natasa Josipovic 1 , Anne Zirkel 6 , Aoife O'Connell 7 , Gary Loughran 7 , James Keane 7 , Audrey Michel 7 , Wolfgang Wagner 8, 9 , Andreas Beyer 5 , Hartmann Harz 4 , Heinrich Leonhardt 4 , Grazvydas Lukinavicius 10 , Christoforos Nikolaou 2 , Argyris Papantonis 1, 3
Aging Cell ( IF 8.0 ) Pub Date : 2024-01-09 , DOI: 10.1111/acel.14083 Spiros Palikyras 1 , Konstantinos Sofiadis 1 , Athanasia Stavropoulou 2 , Adi Danieli-Mackay 1, 3 , Vassiliki Varamogianni-Mamatsi 1 , David Hörl 4 , Simona Nasiscionyte 4 , Yajie Zhu 1 , Ioanna Papadionysiou 1 , Antonis Papadakis 5 , Natasa Josipovic 1 , Anne Zirkel 6 , Aoife O'Connell 7 , Gary Loughran 7 , James Keane 7 , Audrey Michel 7 , Wolfgang Wagner 8, 9 , Andreas Beyer 5 , Hartmann Harz 4 , Heinrich Leonhardt 4 , Grazvydas Lukinavicius 10 , Christoforos Nikolaou 2 , Argyris Papantonis 1, 3
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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.
中文翻译：
通过小分子抑制剂快速同步化学诱导复制样衰老
细胞衰老被认为是机体衰老和晚年疾病的关键因素。尽管体外衰老研究很流行，但由于细胞进入衰老的时间延长且异步，以及其旁分泌效应，可能会变得复杂。为了解决这些问题，我们重新利用了一种小分子抑制剂，inflachromene (ICM)，来诱导人类原代细胞衰老。 ICM 处理后 6 天内，IMR90 细胞群中一致诱导衰老标志，包括 HMGB1 和 -B2 的核驱逐。通过生成和比较来自 ICM 诱导和复制衰老的各种高通量数据集，我们发现了这两种状态的高度相似性。但值得注意的是，ICM 抑制与衰老相关的促炎分泌蛋白组，从而减轻大多数旁分泌效应。总之，ICM 快速、同步地诱导衰老样表型，从而可以在不混淆异质性的情况下研究其核心调控程序。
更新日期：2024-01-09
中文翻译：
通过小分子抑制剂快速同步化学诱导复制样衰老
细胞衰老被认为是机体衰老和晚年疾病的关键因素。尽管体外衰老研究很流行，但由于细胞进入衰老的时间延长且异步，以及其旁分泌效应，可能会变得复杂。为了解决这些问题，我们重新利用了一种小分子抑制剂，inflachromene (ICM)，来诱导人类原代细胞衰老。 ICM 处理后 6 天内，IMR90 细胞群中一致诱导衰老标志，包括 HMGB1 和 -B2 的核驱逐。通过生成和比较来自 ICM 诱导和复制衰老的各种高通量数据集，我们发现了这两种状态的高度相似性。但值得注意的是，ICM 抑制与衰老相关的促炎分泌蛋白组，从而减轻大多数旁分泌效应。总之，ICM 快速、同步地诱导衰老样表型，从而可以在不混淆异质性的情况下研究其核心调控程序。
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