A pivotal discovery in aging research by a Chinese Academy of Sciences (CAS) team has shown that metformin, commonly used for type 2 diabetes, can alleviate cellular senescence, markedly slowing down the aging process in primates. This breakthrough offers fresh insights into aging biology and holds promise for developing interventions for human aging.

Is aging reversible? This timeless question has now found an answer in the laboratories of scientists from CAS. A collaborative study between Liu Guanghui’s team from CAS’s Institute of Zoology, Zhang Weiqi’s team from CAS’s Beijing Institute of Genomics (China National Center for Bioinformation), and Qu Jing’s team from CAS’s Institute of Zoology, has been published in Cell. The research confirms the potential of metformin in combating aging in primates.

Aging is characterized by a decline in organ function and an increased risk of various diseases. To reduce the strain on healthcare systems, scientists have been searching for effective methods to delay aging. The Macaca fascicularis, with its physiological and functional similarities to humans, serves as an excellent model for aging studies.

Metformin slows brain aging in primates. [IMAGE: LIU GUANGHUI’S LAB]

In this study, the researchers employed a multidisciplinary approach, including physiological assessments, medical imaging, multi-parameter blood tests, multi-tissue pathological analysis, and multi-omics, to monitor the metformin-treated male monkeys over 40 months. The findings reveal that extended metformin therapy yielded Gero protective benefits, notably mitigating brain cortex atrophy, boosting cognitive abilities, slowing periodontal bone deterioration, and augmenting the preservation of various tissues and organs, including the liver, heart, lungs, intestines, and muscle tissue.

The study revealed that metformin’s protective effect against aging is independent of its traditional role in blood sugar and metabolic regulation. It acts directly on neurons, activating the Nrf2-mediated antioxidant gene expression network, thereby delaying cellular aging. This finding provides a scientific basis for the Gero protective mechanism of metformin and guides the development of aging intervention drugs.

The research team also utilized machine learning models to build a multi-dimensional primate tissue and organ aging assessment model, accurately evaluating the systemic effects of metformin in delaying aging. The study found that metformin can reduce biological age indicators in primates, including multi-tissue DNA methylation age and transcriptome age, as well as plasma protein and metabolite age, with the most pronounced effect being up to six years, equivalent to 18 human years. This Gero protective effect was particularly significant in the frontal lobe area of the brain and the liver. High-precision single-cell aging clock assessments showed that metformin significantly delayed the aging process of various nerve cells in the brain and hepatocytes in the liver, effectively slowing down the aging speed of these cells by 5 to 6 years, equivalent to approximately 15 to 18 years in human terms.

This study not only injects new vitality into the field of aging intervention but also establishes new paradigms and standards for evaluating the efficacy and safety of human aging interventions. It signifies an important step forward in the quest to delay human aging, with geriatric medicine research gradually shifting focus from treating individual chronic diseases to systemic intervention against aging. Metformin may emerge as a vital tool in the battle against human aging, opening new pathways for the prevention and treatment of aging-related diseases.

Liu Guanghui, a researcher at CAS’s Institute of Zoology, Zhang Weiqi, a researcher at CAS’s Beijing Institute of Genomics, and Qu Jing, a researcher at CAS’s Institute of Zoology, are the co-corresponding authors of this paper. Yang Yuanhan, a doctoral student at CAS’s Institute of Zoology, Lu Xiaoyong, a master’s student at CAS’s Beijing Institute of Genomics, Liu Ning, a researcher at CAS’s Institute of Biophysics, Ma Shuai, an associate researcher at CAS’s Institute of Zoology, Zhang Hui, an assistant researcher at the Second Hospital of Capital Medical University, and Zhang Zhiyi, an associate researcher at CAS’s Institute of Biophysics, are the co-first authors of the paper.

For more information, please contact:

Professor Liu Guanghui

E-mail: ghliu@ioz.ac.cn

Professor Qu Jing

E-mail: qujing@ioz.ac.cn

Institute of Zoology,

Chinese Academy of Sciences

Professor Zhang Weiqi

E-mail: zhangwq@big.ac.cn

Beijing Institute of Genomics,

Chinese Academy of Sciences

Sources: Institute of Zoology,

and Beijing Institute of Genomics,

Chinese Academy of Sciences