Metformin decelerates aging clock in male monkeys

IF 45.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Pub Date : 2024-09-12 DOI:10.1016/j.cell.2024.08.021

Yuanhan Yang, Xiaoyong Lu, Ning Liu, Shuai Ma, Hui Zhang, Zhiyi Zhang, Kuan Yang, Mengmeng Jiang, Zikai Zheng, Yicheng Qiao, Qinchao Hu, Ying Huang, Yiyuan Zhang, Muzhao Xiong, Lixiao Liu, Xiaoyu Jiang, Pradeep Reddy, Xueda Dong, Fanshu Xu, Qiaoran Wang, Guang-Hui Liu

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Abstract

In a rigorous 40-month study, we evaluated the geroprotective effects of metformin on adult male cynomolgus monkeys, addressing a gap in primate aging research. The study encompassed a comprehensive suite of physiological, imaging, histological, and molecular evaluations, substantiating metformin’s influence on delaying age-related phenotypes at the organismal level. Specifically, we leveraged pan-tissue transcriptomics, DNA methylomics, plasma proteomics, and metabolomics to develop innovative monkey aging clocks and applied these to gauge metformin’s effects on aging. The results highlighted a significant slowing of aging indicators, notably a roughly 6-year regression in brain aging. Metformin exerts a substantial neuroprotective effect, preserving brain structure and enhancing cognitive ability. The geroprotective effects on primate neurons were partially mediated by the activation of Nrf2, a transcription factor with anti-oxidative capabilities. Our research pioneers the systemic reduction of multi-dimensional biological age in primates through metformin, paving the way for advancing pharmaceutical strategies against human aging.

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二甲双胍让雄猴的衰老时钟减速

在一项为期40个月的严格研究中，我们评估了二甲双胍对成年雄性眼镜猴的老年保护作用，填补了灵长类动物衰老研究的空白。这项研究涵盖了一整套生理、成像、组织学和分子评估，证实了二甲双胍在机体水平上延缓衰老相关表型的影响。具体来说，我们利用泛组织转录组学、DNA甲基组学、血浆蛋白质组学和代谢组学来开发创新的猴子衰老时钟，并应用这些方法来衡量二甲双胍对衰老的影响。研究结果表明，二甲双胍显著减缓了衰老指标，尤其是大脑衰老的速度大约减缓了6年。二甲双胍具有显著的神经保护作用，能保护大脑结构并提高认知能力。二甲双胍对灵长类神经元的老年保护作用部分是通过激活具有抗氧化能力的转录因子Nrf2来实现的。我们的研究开创了通过二甲双胍系统性降低灵长类动物多维生物年龄的先河，为推进抗人类衰老的药物策略铺平了道路。

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来源期刊

Cell 生物-生化与分子生物学

CiteScore

110.00

自引率

0.80%

发文量

396

审稿时长

2 months

期刊介绍： Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO). The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries. In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.