Research Paper Volume 11, Issue 17 pp 7242—7256
Reactive oxygen species-mediated senescence is accelerated by inhibiting Cdk2 in Idh2-deficient conditions
- 1 School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea
- 2 School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea
- 3 Futuristic Animal Resource and Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju-si, Chungcheongbuk-do, Republic of Korea
- 4 National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju-si, Chungcheongbuk-do, Republic of Korea
- 5 College of Medicine, Chungbuk National University, Cheongju-si, Chungcheongbuk-do, Republic of Korea
- 6 Department of Radiology, Chungbuk National University Hospital, Cheongju-si, Chungcheongbuk-do, Republic of Korea
- 7 Research Institute, e-biogen Inc., Seoul, Republic of Korea
received: January 21, 2019 ; accepted: September 2, 2019 ; published: September 10, 2019 ;https://doi.org/10.18632/aging.102259
How to Cite
Copyright © 2019 Chae et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Among the many factors that promote cellular senescence, reactive oxygen species (ROS) are a focus of intense research because of their critical role in accelerating cellular senescence and initiating senescence-related diseases that can be fatal. Therefore, maintaining the proper balance of ROS in cells is a key method to alleviate senescence. Recent studies have found that isocitrate dehydrogenase 2 (IDH2), a critical enzyme of the tricarboxylic acid cycle, participates in ROS generation and in cellular dysfunction that is induced by excessive levels of ROS. Loss of IDH2 induces mitochondrial dysfunction that promotes excessive ROS generation and the development of several diseases. The results of this study suggest that Idh2 plays an important role in cellular senescence. Idh2 deficiency resulted in senescence-associated phenotypes and increased levels of senescence marker proteins in mouse embryonic fibroblasts and tissues. Furthermore, excessive ROS were generated in Idh2-deficient conditions, promoting cellular senescence by inducing cell cycle arrest through cyclin-dependent kinase 2. These results indicate that loss of Idh2 is a critical factor in regulating cellular senescence. Taken together, our findings contribute to the field of senescence research and suggest that IDH2 is a potential target of future anti-senescence studies.
Idh2: Isocitrate dehydrogenase 2; ROS: Reactive Oxygen Species; Cdk2: Cyclin-dependent kinase 2; α-KG: α-ketoglutarate; MEF: Mouse embryonic fibroblast; BrdU: Bromodeoxyuridine; H&E staining: Hematoxylin and Eosin staining; NAC: N-acetyl cysteine.