探索糖尿病对衰老的影响:TERT 和 COL1A1 甲基化的启示。

Turkish journal of biology = Turk biyoloji dergisi Pub Date : 2024-06-26 eCollection Date: 2024-01-01 DOI:10.55730/1300-0152.2701
Jessica Nathania Liamri, Farizky Martriano Humardani, Giovani Chandra, Lisa Thalia Mulyanata, Tjie Kok, Fenny Irawati, Hikmawan Wahyu Sulistomo, Christoph Reichetzeder, Sulistyo Emantoko Dwi Putra
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引用次数: 0

摘要

背景/目的:衰老是一个多方面的生物过程,会导致身体机能下降,尤其是患有糖尿病的老年人,他们的生理年龄与实际年龄明显不符。大量研究表明,糖尿病会加速细胞和器官的衰老。与端粒长度有关的端粒酶逆转录酶(TERT)和皮肤胶原蛋白的主要成分 1 型链胶原蛋白(COL1A1)是显著的衰老标志物。此外,通过甲基化分析发现,与年龄有关的甲基化也会增加,从而加剧衰老。然而,衰老与糖尿病之间的详细相互作用,尤其是甲基化方面的相互作用,仍未得到充分探索,值得进一步研究,以阐明两者之间的生物学联系:在本研究中,我们以瑞士韦伯斯特品系小鼠为糖尿病模型,阐明了糖尿病对衰老过程的调节作用,特别关注肾脏中 TERT 和皮肤中 COL1A1 的变化。样本被分为三个不同的年代组:年代年轻组(16 周;n = 5)、年代年长组(40 周;n = 5)和定期评估组(16 周;n = 30),每周系统地从中牺牲 5 只小鼠:结果:我们的研究结果表明,糖尿病对 TERT 和 COL1A1 的甲基化状态有明显影响,其特点是周期组(第 1-6 周)的甲基化水平升高,同时 TERT 和 COL1A1 基因的表达逐渐减弱:结论:观察到的 TERT 和 COL1A1 甲基化水平的改变提出了一个假设,即糖尿病可能加速衰老过程,同时影响 TERT 和 COL1A 的产生,表面上看是通过启动子基因高甲基化的机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Exploring the impact of diabetes on aging: insights from TERT and COL1A1 methylation.

Background/aim: Aging, a multifaceted biological process, leads to diminished physical performance, especially in older adults with diabetes, where a mismatch between biological and chronological age is noticeable. Numerous studies have demonstrated that diabetes accelerates aging at the cellular and organ levels. Notable aging markers are telomerase reverse transcriptase (TERT), related to telomere length, and type 1 chain collagen (COL1A1), a key component of skin collagen. Additionally, age-related methylation increases, as revealed through methylation analysis, augmenting aspects of aging. However, the detailed interplay between aging and diabetes, particularly regarding methylation, remains underexplored and warrants further study to elucidate the biological links between the two.

Materials and methods: In this study, we elucidate the modulatory influence of diabetes on the aging process, focusing specifically on the modifications in TERT in the kidney and COL1A1 in the skin using mice of Swiss Webster strain as the diabetes model. Specimens were categorized into three distinct chronological cohorts: chronologically young (16 weeks; n = 5), chronologically old (40 weeks; n = 5), and a periodically assessed group (16 weeks; n = 30), from which five mice were systematically sacrificed on a weekly basis.

Results: Our findings reveal a marked impact of diabetes on the methylation statuses of TERT and COL1A1, characterized by an elevation in methylation levels within the periodic group (1st-6th week) and a simultaneous, progressive attenuation in the expression of TERT and COL1A1 genes.

Conclusion: The observed alterations in the methylation levels of TERT and COL1A1 propound the hypothesis that diabetes potentially expedites the aging process, concomitantly impinging on the production of TERT and COL1A, ostensibly through the mechanism of promoter gene hypermethylation.

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