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CO ameliorates cellular senescence and aging by modulating the miR-34a/Sirt1 pathway

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Authors
Park, Jeongmin; Kim, Jin; Chen, Yingqing; Song, Hyun-Chul; Chen, Yubing; Zheng, Min; Surh, Young-Joon; Kim, Uh-Hyun; Park, Jeong Woo; Joe, Yeonsoo; Chung, Hun Taeg
Issue Date
2020-01
Citation
Free Radical Research
Keywords
Caenorhabditis eleganscarbon monoxidehaemoxygenasemiR-34aoxidative stresssenescence-associated secretory phenotypeSirt1
Abstract
Oxidative stress is recognised as a key factor that can lead to cellular senescence and aging. Carbon monoxide (CO) is produced by haemoxygenase-1 (HO-1), which exerts cytoprotective effects in aging-related diseases, whereas the effect of CO on cellular senescence and aging has not been elucidated. In the current study, we clearly demonstrated that CO delays the process of cellular senescence and aging through regulation of miR-34a and Sirt1 expression. CO reduced H2O2-induced premature senescence in human diploid fibroblast WI-38 cells measured with SA-beta-Gal-staining. Furthermore, CO significantly decreased the expression of senescence-associated secretory phenotype (SASP), including TNF-alpha IL-6, and PAI-1 and increased the transcriptional levels of antioxidant genes, such as HO-1 and NQO1. Moreover, CO apparently enhanced the expression of Sirt1 through down-regulation of miR-34a. Next, to determine whether Sirt1 mediates the inhibitory effect of CO on cellular senescence, we pre-treated WI-38 cells with the Sirt1 inhibitor Ex527 and a miR-34a mimic followed by the administration of H2O2 and evaluated the expression of SASP and antioxidant genes as well as ROS production. According to our results, Sirt1 is crucial for the antiaging and antioxidant effects of CO. Finally, CO prolonged the lifespan of Caenorhabditis elegans and delayed high-fat diet-induced liver aging. Taken together, these findings demonstrate that CO reduces cellular senescence and liver aging through the regulation of miR-34a and Sirt1.
ISSN
1071-5762
URI
https://hdl.handle.net/10371/172732
DOI
https://doi.org/10.1080/10715762.2019.1710142
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Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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