PRDM16通过上调GSTM1来减缓细胞衰老。

IF 14.1 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Qian Yuan, Yuting Zhu, Ben Tang, Yaru Xie, Mingcun Hu, Hua Su, Youhua Liu, Chun Zhang
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引用次数: 0

摘要

细胞衰老是衰老的标志,衰老细胞(SnCs)的积累加速了衰老过程,导致与衰老相关的器官疾病。PRDF1和RIZ1同源结构域(PRDM)蛋白表现出强大的转录调控活性,并控制着广泛的生物过程。然而,其在细胞衰老中的作用尚不清楚。本研究表明,与年轻小鼠相比,PRDM蛋白家族成员PRDM16在老年小鼠的多个器官中显著减少。Prdm16的全局性缺失导致肾、心、肺、海马、胃和肠道等多个器官的细胞衰老,导致与衰老相关的器官损伤加速。此外,小管特异性Prdm16缺失加重了缺血再灌注手术后受辐照小鼠辐照诱导的肾脏衰老和衰老相关肾脏疾病。通过慢病毒外源性传递PRDM16基因,可有效延缓体内外细胞衰老。在机制上,PRDM16改善谷胱甘肽代谢,抑制DNA氧化损伤,这是衰老的驱动力。具体来说,PRDM16通过结合谷胱甘肽s -转移酶1 (GSTM1)的启动子区域上调其转录。转染GSTM1可逆转PRDM16缺乏诱导的细胞衰老和肾脏老化。总的来说,这些结果为研究抗衰老疗法提供了一个潜在的目标。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
PRDM16 Reduces Cellular Senescence by Upregulating GSTM1.

Cellular senescence is a hallmark of aging and the accumulation of senescent cells (SnCs) accelerates the aging process, contributing to aging-related organ disorders. The PRDF1 and RIZ1 homology domain (PRDM) protein exhibits robust transcriptional regulatory activities and governs a wide range of biological processes. However, its roles in cellular senescence remain unclear. Here, this work demonstrates that PRDM16, a member of the PRDM protein family, decreases significantly in multiple organs of aged mice compared to young mice. Global Prdm16 deletion contributes to cellular senescence in various organs, including the kidneys, heart, lungs, hippocampus, stomach, and gut, leading to accelerated aging-related organ injury. Furthermore, tubular-specific Prdm16 deletion aggravates irradiation-induced kidney aging and aging-related kidney diseases in irradiated mice subjected to ischemia-reperfusion surgery. Exogenous PRDM16 gene delivery by lentivirus effectively attenuates cellular senescence in vitro and in vivo. Mechanistically, PRDM16 improves glutathione metabolism and inhibits oxidative DNA damage, which is a driving force of senescence. Specifically, PRDM16 upregulates the transcription of glutathione S-transferase mu 1 (GSTM1) by binding to its promoter region. Transfection with GSTM1 reverses PRDM16 deficiency-induced cellular senescence and kidney aging. Collectively, these results provide a potential target for the investigation of anti-aging therapies.

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来源期刊
Advanced Science
Advanced Science CHEMISTRY, MULTIDISCIPLINARYNANOSCIENCE &-NANOSCIENCE & NANOTECHNOLOGY
CiteScore
18.90
自引率
2.60%
发文量
1602
审稿时长
1.9 months
期刊介绍: Advanced Science is a prestigious open access journal that focuses on interdisciplinary research in materials science, physics, chemistry, medical and life sciences, and engineering. The journal aims to promote cutting-edge research by employing a rigorous and impartial review process. It is committed to presenting research articles with the highest quality production standards, ensuring maximum accessibility of top scientific findings. With its vibrant and innovative publication platform, Advanced Science seeks to revolutionize the dissemination and organization of scientific knowledge.
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