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尿石素A通过SIRT1调节PER2降解并增强人类衰老细胞中生物钟的振幅。

Urolithin A Modulates PER2 Degradation via SIRT1 and Enhances the Amplitude of Circadian Clocks in Human Senescent Cells.

作者信息

Kuatov Rassul, Takano Jiro, Arie Hideyuki, Kominami Masaru, Tateishi Norifumi, Wakabayashi Ken-Ichi, Takemoto Daisuke, Izumo Takayuki, Nakao Yoshihiro, Nakamura Wataru, Shinohara Kazuyuki, Nakahata Yasukazu

机构信息

Department of Neurobiology & Behavior, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan.

Institute for Science of Life, Suntory Wellness Limited, Kyoto 619-0284, Japan.

出版信息

Nutrients. 2024 Dec 25;17(1):20. doi: 10.3390/nu17010020.

DOI:10.3390/nu17010020
PMID:39796454
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11722880/
Abstract

BACKGROUND/OBJECTIVES: Circadian clocks are endogenous systems that regulate numerous biological, physiological, and behavioral events in living organisms. Aging attenuates the precision and robustness of circadian clocks, leading to prolonged and dampened circadian gene oscillation rhythms and amplitudes. This study investigated the effects of food-derived polyphenols such as ellagic acid and its metabolites (urolithin A, B, and C) on the aging clock at the cellular level using senescent human fibroblast cells, TIG-3 cells.

METHODS

Lentivirus-infected TIG-3 cells expressing Bmal1-luciferase were used for real-time luciferase monitoring assays.

RESULTS

We revealed that urolithins boosted the amplitude of circadian gene oscillations at different potentials; urolithin A (UA) amplified the best. Furthermore, we discovered that UA unstabilizes PER2 protein while stabilizing SIRT1 protein, which provably enhances oscillation.

CONCLUSIONS

The findings suggest that urolithins, particularly UA, have the potential to modulate the aging clock and may serve as therapeutic nutraceuticals for age-related disorders associated with circadian dysfunction.

摘要

背景/目的：生物钟是调节生物体中众多生物、生理和行为事件的内源性系统。衰老会削弱生物钟的精确性和稳健性，导致昼夜节律基因振荡的周期延长且振幅减弱。本研究使用衰老的人类成纤维细胞TIG-3细胞，在细胞水平上研究了诸如鞣花酸及其代谢产物（尿石素A、B和C）等食物来源的多酚对衰老生物钟的影响。

方法

使用表达Bmal1-荧光素酶的慢病毒感染TIG-3细胞进行实时荧光素酶监测分析。

结果

我们发现尿石素在不同程度上增强了昼夜节律基因振荡的振幅；尿石素A（UA）增强效果最佳。此外，我们发现UA会使PER2蛋白不稳定，同时使SIRT1蛋白稳定，这可证实增强了振荡。

结论

研究结果表明，尿石素，尤其是UA，有调节衰老生物钟的潜力，可能作为与昼夜节律功能障碍相关的年龄相关疾病的治疗性营养保健品。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1396/11722880/2ac59ce64c29/nutrients-17-00020-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1396/11722880/c05ea32d1f12/nutrients-17-00020-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1396/11722880/e05c7ff51525/nutrients-17-00020-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1396/11722880/eae2cc6cea9a/nutrients-17-00020-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1396/11722880/3cd715b0ff60/nutrients-17-00020-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1396/11722880/736c4ef6286b/nutrients-17-00020-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1396/11722880/bbe61d95736e/nutrients-17-00020-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1396/11722880/2ac59ce64c29/nutrients-17-00020-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1396/11722880/c05ea32d1f12/nutrients-17-00020-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1396/11722880/e05c7ff51525/nutrients-17-00020-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1396/11722880/eae2cc6cea9a/nutrients-17-00020-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1396/11722880/3cd715b0ff60/nutrients-17-00020-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1396/11722880/736c4ef6286b/nutrients-17-00020-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1396/11722880/bbe61d95736e/nutrients-17-00020-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1396/11722880/2ac59ce64c29/nutrients-17-00020-g007.jpg

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