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探索糖尿病对衰老的影响:来自端粒酶逆转录酶(TERT)和I型胶原蛋白α1链(COL1A1)甲基化的见解。

Exploring the impact of diabetes on aging: insights from TERT and COL1A1 methylation.

作者信息

Liamri Jessica Nathania, Humardani Farizky Martriano, Chandra Giovani, Mulyanata Lisa Thalia, Kok Tjie, Irawati Fenny, Sulistomo Hikmawan Wahyu, Reichetzeder Christoph, Dwi Putra Sulistyo Emantoko

机构信息

Faculty of Biotechnology, University of Surabaya, Surabaya, Indonesia.

Department of Biomedical Science, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia.

出版信息

Turk J Biol. 2024 Jun 26;48(4):257-266. doi: 10.55730/1300-0152.2701. eCollection 2024.

Abstract

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.

摘要

背景/目的:衰老作为一个多方面的生物学过程,会导致身体机能下降,在患有糖尿病的老年人中尤为明显,这些人的生物学年龄与实际年龄不匹配。大量研究表明,糖尿病会在细胞和器官水平加速衰老。显著的衰老标志物包括与端粒长度相关的端粒酶逆转录酶(TERT)和皮肤胶原蛋白的关键成分I型胶原蛋白α1链(COL1A1)。此外,通过甲基化分析发现,与年龄相关的甲基化增加,加剧了衰老的各个方面。然而,衰老与糖尿病之间的详细相互作用,特别是关于甲基化的相互作用,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。

材料与方法

在本研究中,我们以瑞士韦伯斯特品系小鼠作为糖尿病模型,阐明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的修饰。样本被分为三个不同的实际年龄组:实际年龄较小(16周;n = 5)、实际年龄较大(40周;n = 5)以及一个定期评估组(16周;n = 30),每周从该组中系统地处死5只小鼠。

结果

我们的研究结果显示,糖尿病对TERT和COL1A1的甲基化状态有显著影响,其特征是在定期评估组(第1 - 6周)中甲基化水平升高,同时TERT和COL1A1基因的表达逐渐减弱。

结论

观察到的TERT和COL1A1甲基化水平的变化提出了一个假设,即糖尿病可能通过启动子基因高甲基化机制加速衰老过程,同时影响TERT和COL1A的产生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b19b/11407328/175338c84e98/tjb-48-04-257f1.jpg

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