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

CO ameliorates cellular senescence and aging by modulating the miR-34a/Sirt1 pathway. Free Radic Res. 2020 Mar 31;:1-11 Authors: Park J, Kim J, Chen Y, Song HC, Chen Y, Zheng M, Surh YJ, Kim UH, Park JW, Joe Y, Chung HT 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-β-Gal-staining. Furthermore, CO significantly decreased the expression of senescence-associated secretory phenotype (SASP), including TNF-α 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...
Source: Free Radical Research - Category: Research Tags: Free Radic Res Source Type: research

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