Abstract
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.
Highlights
Senescence, called biological aging, is a functional degradation process of cells and tissues [1], and oxidative stress and free radicals are two critical elements that induce senescence [2]
Protein and mRNA levels of Isocitrate dehydrogenase 2 (Idh2) are decreased in Passage 8 (P8) Mouse embryonic fibroblast (MEF) (Figure 1D)
We examined the effects of Idh2 deficiency in cellular senescence, which accelerates aging
Summary
Senescence, called biological aging, is a functional degradation process of cells and tissues [1], and oxidative stress and free radicals are two critical elements that induce senescence [2]. Accumulation of oxidative stress in cells and tissues causes several age-related diseases that shorten the life span of the organism [3]. Reactive oxygen species (ROS) are a byproduct of normal mitochondrial respiration, the oxidative www.aging-us.com phosphorylation pathway that activates the production of various superoxides [4]. Superoxide dismutase converts superoxides to hydrogen peroxide (H2O2), which participates in cellular signaling pathways. Maintaining the balance of ROS formation is important for cellular homeostasis [5]. Excessive ROS formation can induce oxidative stress, which plays a critical role in the development of various diseases, including aging [6]
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