Metformin decelerates aging clock in male monkeys.

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

Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Membrane Biology, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Membrane Biology, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. · pubmed

Paper

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.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper is relevant to longevity research as it investigates the geroprotective effects of metformin on aging in primates, addressing the root causes of aging rather than merely treating age-related diseases. The comprehensive approach, including multi-dimensional biological age assessments and the identification of mechanisms like Nrf2 activation, contributes important findings that advance the understanding of aging interventions. However, while the results are significant, they may not yet represent a major breakthrough with transformative implications for the field, hence the score of 6.

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