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白藜芦醇在早衰细胞中的RNA m6A甲基化调控机制

RNA m6A methylation regulatory mechanism of resveratrol in premature senescence cells.

作者信息

Zhang Xinyu, Zhu Chenyu, Zhang Luyun, Tan Luyi, Cheng Wenli, Li Min, Zhang Xingtan, Zhang Wenjuan, Zhang Wenji

机构信息

Department of Public Health and Preventive Medicine, School of Medicine Jinan University Guangzhou Guangdong People's Republic of China.

Key Laboratory of Crop Genetic Improvement of Guangdong Province Crops Research Institute, Guangdong Academy of Agricultural Sciences Guangzhou Guangdong People's Republic of China.

出版信息

Food Sci Nutr. 2024 Sep 30;12(11):9238-9251. doi: 10.1002/fsn3.4487. eCollection 2024 Nov.

Abstract

Resveratrol, a natural compound found in various plants, is known for its anti-inflammatory, antioxidant, and senescence-delaying properties. RNA N6-methyladenosine (m6A) methylation plays a crucial role in oxidative stress and premature cellular senescence processes and is closely associated with age-related disorders. However, the anti-premature senescence via RNA m6A methylation mechanism of resveratrol is still not fully understood. In this study, based on premature senescence model of human embryonic lung fibroblasts (HEFs) induced by hydrogen peroxide (HO), a widely accepted model of premature senescence caused by oxidative stress, we explored the anti-aging regulatory effects of resveratrol at the RNA m6A methylation level. Our data suggested that resveratrol significantly delayed premature senescence by increasing cell viability, reducing SA-β-gal blue staining rate, ROS levels, and senescence-associated secretory phenotypes (SASP) expression in HEFs. Meanwhile, resveratrol increased the whole RNA methyltransferases activity and the overall m6A level during senescence. Furthermore, three genes , , and have been identified as the main ones regulating premature by resveratrol. Specifically, it decreased , RNA m6A methylation level, and increased level in premature cells. Our study provided new clues for exploring the mechanism and application of resveratrol in the field of premature aging.

摘要

白藜芦醇是一种在多种植物中发现的天然化合物,以其抗炎、抗氧化和延缓衰老的特性而闻名。RNA N6-甲基腺苷(m6A)甲基化在氧化应激和细胞早衰过程中起关键作用,且与年龄相关疾病密切相关。然而,白藜芦醇通过RNA m6A甲基化机制抗早衰的作用仍未完全明确。在本研究中,基于过氧化氢(H₂O₂)诱导的人胚肺成纤维细胞(HEFs)早衰模型(一种广泛认可的由氧化应激导致早衰的模型),我们在RNA m6A甲基化水平上探究了白藜芦醇的抗衰老调控作用。我们的数据表明,白藜芦醇通过提高细胞活力、降低SA-β-半乳糖苷酶蓝色染色率、活性氧水平以及衰老相关分泌表型(SASP)表达,显著延缓了HEFs的早衰。同时,白藜芦醇在衰老过程中提高了整体RNA甲基转移酶活性和总体m6A水平。此外,已确定三个基因,[具体基因名称缺失]为白藜芦醇调控早衰的主要基因。具体而言,它降低了早衰细胞中[具体基因名称缺失]的RNA m6A甲基化水平,并提高了[具体基因名称缺失]水平。我们的研究为探索白藜芦醇在早衰领域的作用机制及应用提供了新线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d16/11606896/d311cb70bc3d/FSN3-12-9238-g004.jpg

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