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牛磺酸通过拮抗内质网应激抑制果蝇衰老相关的肠道增生。

Taurine represses age-associated gut hyperplasia in Drosophila via counteracting endoplasmic reticulum stress.

机构信息

Laboratory for Stem Cell and anti-Aging Research, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.

Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.

出版信息

Aging Cell. 2021 Mar;20(3):e13319. doi: 10.1111/acel.13319. Epub 2021 Feb 9.

Abstract

As they age, adult stem cells become more prone to functional decline, which is responsible for aging-associated tissue degeneration and diseases. One goal of aging research is to identify drugs that can repair age-associated tissue degeneration. Multiple organ development-related signaling pathways have recently been demonstrated to have functions in tissue homeostasis and aging process. Therefore, in this study, we tested several chemicals that are essential for organ development to assess their ability to delay intestinal stem cell (ISC) aging and promote gut function in adult Drosophila. We found that taurine, a free amino acid that supports neurological development and tissue metabolism in humans, represses ISC hyperproliferation and restrains the intestinal functional decline seen in aged animals. We found that taurine represses age-associated ISC hyperproliferation through a mechanism that eliminated endoplasmic reticulum (ER) stress by upregulation of the target genes of unfolded protein response in the ER (UPR ) and inhibiting the c-Jun N-terminal kinase (JNK) signaling. Our findings show that taurine plays a critical role in delaying the aging process in stem cells and suggest that it may be used as a natural compound for the treatment of age-associated, or damage-induced intestinal dysfunction in humans.

摘要

随着年龄的增长,成体干细胞更容易出现功能衰退,这是与衰老相关的组织退化和疾病的原因。衰老研究的一个目标是确定能够修复与年龄相关的组织退化的药物。最近已经证明,与器官发育相关的多个信号通路在组织稳态和衰老过程中具有功能。因此,在这项研究中,我们测试了几种对器官发育至关重要的化学物质,以评估它们延缓肠道干细胞 (ISC) 衰老和促进成年果蝇肠道功能的能力。我们发现,牛磺酸是一种支持人类神经发育和组织代谢的游离氨基酸,它抑制 ISC 的过度增殖,并抑制老年动物中出现的肠道功能下降。我们发现,牛磺酸通过上调内质网 (ER) 中未折叠蛋白反应的靶基因 (UPR) 和抑制 c-Jun N-末端激酶 (JNK) 信号来消除内质网应激,从而抑制与年龄相关的 ISC 过度增殖。我们的研究结果表明,牛磺酸在延缓干细胞衰老过程中起着关键作用,并表明它可能被用作一种天然化合物,用于治疗与年龄相关的或损伤引起的人类肠道功能障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/667f/7963329/b75239d8c6d0/ACEL-20-e13319-g005.jpg

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