中国科学院动物研究所刘光慧等研究人员合作发现，二甲双胍可减缓雄性猴子的衰老时钟。相关论文于2024年9月12日在线发表于国际学术期刊《细胞》。
在一项为期40个月的严谨研究中，研究人员评估了二甲双胍对成年雄性食蟹猴的抗衰老作用，填补了灵长类动物衰老研究的空白。该研究包含全面的生理、影像、组织学和分子评估，证实了二甲双胍在整体水平上延缓与年龄相关表型的影响。
具体而言，研究人员利用全组织转录组学、DNA甲基化组学、血浆蛋白质组学和代谢组学开发了创新的猴子衰老时钟，并应用这些方法评估了二甲双胍对衰老的影响。结果显示衰老指标显著减缓，尤其是在大脑衰老方面大约回退了6年。
二甲双胍对大脑具有显著的神经保护作用，能够维持大脑结构并增强认知能力。其对灵长类动物神经元的抗衰老效果，部分通过激活具有抗氧化功能的转录因子Nrf2来实现。该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途径，为推动针对人类衰老的药物策略提供了新方向。
附：英文原文
Title: Metformin decelerates aging clock in male monkeys
Author: 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, Qian Zhao, Jinghui Lei, Shuhui Sun, Ying Jing, Jingyi Li, Yusheng Cai, Yanling Fan, Kaowen Yan, Yaobin Jing, Amin Haghani, Mengen Xing, Xuan Zhang, Guodong Zhu, Weihong Song, Steve Horvath, Concepcion Rodriguez Esteban, Moshi Song, Si Wang, Guoguang Zhao, Wei Li, Juan Carlos Izpisua Belmonte, Jing Qu, Weiqi Zhang, Guang-Hui Liu
Issue&Volume: 2024-09-12
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.
DOI: 10.1016/j.cell.2024.08.021
Source: https://www.cell.com/cell/abstract/S0092-8674(24)00914-0