Breakthrough Discovery: Metformin Found to Turn Back the Clock on Aging in Primates, Paving the Way for Human Anti-Aging Therapies
- Liu Guanghui's team from the Institute of Zoology, Chinese Academy of Sciences, in collaboration with Zhang Weiqi's team from the Beijing Genomics Institute (National Center for Bioinformatics) and...
- After eight years of exploration, the research team found that metformin can reset the aging clock of primates and significantly delay primate aging, revealing its role in aging.
- Aging is a complex physiological process involving organ dysfunction and the occurrence of multiple diseases.
Metformin Delays Aging in Primates, Study Finds
- Metformin
Source: Biological World 2024-09-17 10:13
This study is the first to draw a drug roadmap for targeting primate aging and is the first to demonstrate the potential of metformin to reverse the primate aging clock.
Liu Guanghui’s team from the Institute of Zoology, Chinese Academy of Sciences, in collaboration with Zhang Weiqi’s team from the Beijing Genomics Institute (National Center for Bioinformatics) and Qu Jing’s team from the Institute of Zoology, Chinese Academy of Sciences, published a paper in a top international academic journal Cell titled: Metformin decelerates aging clock in male monkeys. This 40-month study fills a gap in primate aging research and confirms metformin’s potential for slowing aging in primates.
After eight years of exploration, the research team found that metformin can reset the aging clock of primates and significantly delay primate aging, revealing its role in aging. This finding provides new insights into the biological mechanisms of aging and potential strategies for future interventions in human aging.
Aging is a complex physiological process involving organ dysfunction and the occurrence of multiple diseases. In order to reduce the burden on the medical system, scientists have been exploring effective methods to delay aging. Among many experimental animals, crab-eating macaques have become an ideal model for aging research because of their similarity to human physiological structure and function.
Cutting-edge high-throughput omics technologies allow us to accurately quantify the rate of aging at the molecular level. Using machine learning models to integrate epigenetic, transcriptomic, proteomic and metabolomic data has paved the way for the establishment of an “Aging Clock,” providing a method for evaluating the effectiveness of interventions against aging. In addition, the development of single-cell sequencing technology has also improved our understanding of the complex cellular and molecular basis of the aging process and its interventions.
However, the potential of metformin to promote systemic rejuvenation across multiple different biological dimensions at the pan-tissue level remains to be fully understood.
To explore whether metformin can alleviate age-related functional and structural decline, the research team conducted a comprehensive 40-month study to evaluate metformin supplementation therapy in middle-aged and elderly male crab-eating macaques. Specifically, the study covered a wide range of analytical techniques, including physiological function assessment, medical imaging, multi-parameter blood testing, multi-tissue pathology analysis, and multi-dimensional life-omics, which quantified these parameters and integrated them into a comprehensive “monkey aging clock” to measure the impact of metformin on aging.
The analysis results showed that metformin slowed down the aging process in various tissues of male crab-eating macaques. Specifically, individuals who took metformin for a long time showed obvious aging-delaying effects in reducing cerebral cortical atrophy, improving cognitive function, delaying periodontal bone loss, and protecting multiple tissues and organs such as the liver, heart, lungs, small intestine and skeletal muscle.
Figure 1. Metformin delays brain aging and enhances cognitive function in primates
The research team further found that metformin’s aging-protective effect on primates is independent of its traditional blood sugar and metabolic regulation functions. Metformin acts directly on cells to activate the Nrf2-mediated antioxidant gene expression network, thereby delaying cell aging. This discovery provides a scientific basis for metformin’s aging-protective mechanism and points the way for the development of aging intervention drugs.
More importantly, the study highlights the significant neuroprotective effects of metformin in humans. The protein was further validated in a neuronal aging model.
Figure 2. Metformin delays human neuronal aging
Next, the research team used machine learning models to construct a multidimensional primate tissue and organ aging assessment model to accurately evaluate the systemic effects of metformin in delaying aging.
The results show that metformin can significantly reduce the biological age indicators of primates (including multi-tissue DNA methylation age and transcriptome age, as well as plasma protein and metabolite age), and the effect can reduce the age of primates by up to 6 years (equivalent to humans 18 years). This aging-slowing effect was particularly pronounced in the frontal lobe region of the brain and the liver. In the high-precision aging clock assessment at the single cell level, metformin significantly delayed the aging process of various nerve cells in the brain and hepatocytes in the liver, equivalent to slowing down the aging rate of these cells by 5-6 years (equivalent to 15-18 years in humans).
Figure 3. Metformin resets the multidimensional aging clock in primates
In general, this study has drawn up a drug roadmap for primate aging for the first time, and has been the first to demonstrate the potential of metformin to reverse the primate aging clock. These innovative discoveries have not only injected new vitality into the field of anti-aging, but also provided a new paradigm and standard for evaluating the effectiveness and heterogeneity of human aging interventions, and paved the way for advancing human anti-aging drug strategies, marking an important step forward for humans in delaying aging.
Liu Guanghui, a researcher at the Institute of Zoology, Chinese Academy of Sciences, Zhang Weiqi, a researcher at the Beijing Institute of Genomics, Chinese Academy of Sciences, and Qu Jing, a researcher at the Institute of Zoology, Chinese Academy of Sciences, are the co-corresponding authors of the paper. Yang Yuanhan, a doctoral student at the Institute of Zoology, Chinese Academy of Sciences, Lu Xiaoyong, a master’s student at the Beijing Institute of Genomics, Chinese Academy of Sciences, Liu Ning, a researcher at the Institute of Biophysics, Chinese Academy of Sciences, Ma Shuai, a researcher at the Institute of Zoology/Beijing Institute of Stem Cell and Regenerative Medicine, Zhang Hui, an assistant researcher at Anzhen Hospital of Capital Medical University, and Zhang Yizhi, an associate researcher at the Institute of Biophysics, Chinese Academy of Sciences, are the co-first authors of the paper.