中國(guó)科學(xué)院動(dòng)物研究所劉光慧等研究人員合作發(fā)現(xiàn)，二甲雙胍可減緩雄性猴子的衰老時(shí)鐘。相關(guān)論文于2024年9月12日在線發(fā)表于國(guó)際學(xué)術(shù)期刊《細(xì)胞》。
在一項(xiàng)為期40個(gè)月的嚴(yán)謹(jǐn)研究中，研究人員評(píng)估了二甲雙胍對(duì)成年雄性食蟹猴的抗衰老作用，填補(bǔ)了靈長(zhǎng)類(lèi)動(dòng)物衰老研究的空白。該研究包含全面的生理、影像、組織學(xué)和分子評(píng)估，證實(shí)了二甲雙胍在整體水平上延緩與年齡相關(guān)表型的影響。
具體而言，研究人員利用全組織轉(zhuǎn)錄組學(xué)、DNA甲基化組學(xué)、血漿蛋白質(zhì)組學(xué)和代謝組學(xué)開(kāi)發(fā)了創(chuàng)新的猴子衰老時(shí)鐘，并應(yīng)用這些方法評(píng)估了二甲雙胍對(duì)衰老的影響。結(jié)果顯示衰老指標(biāo)顯著減緩，尤其是在大腦衰老方面大約回退了6年。
二甲雙胍對(duì)大腦具有顯著的神經(jīng)保護(hù)作用，能夠維持大腦結(jié)構(gòu)并增強(qiáng)認(rèn)知能力。其對(duì)靈長(zhǎng)類(lèi)動(dòng)物神經(jīng)元的抗衰老效果，部分通過(guò)激活具有抗氧化功能的轉(zhuǎn)錄因子Nrf2來(lái)實(shí)現(xiàn)。該研究開(kāi)創(chuàng)了通過(guò)二甲雙胍，系統(tǒng)性降低靈長(zhǎng)類(lèi)動(dòng)物多維生物年齡的途徑，為推動(dòng)針對(duì)人類(lèi)衰老的藥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
期刊信息
Cell：《細(xì)胞》，創(chuàng)刊于1974年。隸屬于細(xì)胞出版社，最新IF：66.85
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