Why do we age? How old are we really? How to age healthily? This is the topic discussed by basic research scientists and clinical doctors at the recent Xiangshan Science Conference. The above questions correspond to three scientific issues: aging mechanism, aging measurement, and aging intervention Liu Guanghui, one of the executive chairmen of the meeting and a researcher from the Institute of Zoology of the Chinese Academy of Sciences, pointed out that at present, relevant research is facing challenges such as lack of targets, difficulty in early warning and poor intervention. At the conference on the theme of "Mechanisms and Interventions of Aging", experts called for strengthening the basic research of aging biology, promoting the clinical application of related technologies, and ultimately achieving healthy aging - aging without aging, aging with less disease. Human aging is a complex and integral process. By the end of 2023, there will be 297 million people aged 60 and above in China, accounting for 21.1% of the national population. It is expected that by around 2050, the population aged 60 and above in China will reach 480 million, accounting for a quarter of the global elderly population. China's aging population is large in scale, fast in development, and the situation is grim. It is particularly urgent to study the mechanism of aging and scientific prevention and control. Is aging a disease? Some people believe that aging is a physiological phenomenon that naturally evolves with age; Some people believe that aging is a progressive, degenerative disease; Some people also believe that aging itself is not a disease, but aging can bring diseases; Some people believe that whether aging is a disease depends on the degree of aging, and premature aging is a disease. In fact, in 2018, the World Health Organization defined aging as a new disease and promoted research on aging interventions globally. Aging is a cutting-edge field in life science research and an important area in biomedical research Pei Gang, one of the executive chairmen of the meeting and an academician of the CAS Member, believes that aging is closely related to many diseases. Grasping the key point of aging and deeply studying its mechanism is expected to provide a new breakthrough for the treatment of major diseases. Aging involves multiple organs in the human body. Which organ ages first? Aging is a complex nonlinear biological process that spans multiple levels such as molecules, cells, and organs. Aging in different organs has asynchrony, and aging in different cells of the same organ also has heterogeneity, "said Liu Guanghui. This asynchrony and heterogeneity increase the difficulty of research. At present, the scientific community is still actively exploring which organ in the human body will show signs of aging first. Aging involves multiple systems such as hematopoiesis, immunity, cardiovascular, nervous, respiratory, digestive, endocrine, and reproductive systems Ju Zhenyu, Dean of the Institute of Aging and Regenerative Medicine at Jinan University, believes that human aging is a holistic process, and there are both commonalities and individual differences among various systems. Therefore, it is necessary to comprehensively analyze its mechanisms from multiple dimensions. Aging can be quantified to some extent. When people have a cold or fever, they will measure their body temperature and check their blood routine. So, how should aging be scientifically measured? Aging is the accumulation of damage caused by the body's own and external factors during the aging process, leading to functional decline, chronic diseases, and ultimately death Wang Yanjiang, chief physician of the neurology department at the Army Medical University Army Characteristic Medical Center (Daping Hospital), said that accurately measuring aging is a major scientific problem that urgently needs to be solved. In order to effectively evaluate the degree of aging of individuals and provide precise basis for intervention in aging and related diseases, it is very important to find suitable aging biomarkers. Wang Yanjiang introduced that aging biomarkers need to have three characteristics: first, they will be manifested in the process of healthy aging; Secondly, exacerbating its degree of change will accelerate aging; Thirdly, alleviating its degree of change can delay or reverse aging, thereby extending lifespan. Internationally, research programs targeting aging biomarkers have been launched one after another. Scholars have proposed 12 major characteristics of aging, such as cellular aging, chronic inflammation, and ecological disorders, from three levels: the causes of injury, the response to injury, and the phenotype of injury. They have also studied aging biomarkers and biological age clocks from genetic, molecular, structural, and functional perspectives. China established the Aging Biomarker Consortium (ABC) in December 2022, which collaborates with domestic scholars to conduct research on aging biomarkers. The establishment of the consortium has been carefully considered and prepared, bringing together professionals from various fields to build a scientific measurement system for aging that is' clear and practical ', "said Pei Gang. Under the organization of the China Aging Markers Research Consortium, Chinese scientists have preliminarily outlined the global landscape of aging research. Related scholars have successively developed a framework of aging biomarkers for the brain, heart, blood vessels, liver, and bones from three levels: body fluids, imaging, and function. The framework of aging biomarkers for other tissues and organs is also being developed, laying the foundation for the study of multi system aging biomarkers throughout the body, "said Wang Yanjiang. Although China has made significant progress in the research of aging biomarkers, there are still many major issues that need to be addressed. Wang Yanjiang believes that in the future, a natural aging population cohort should be further established to provide strong sample support for the study of aging biomarkers; At the same time, it is necessary to strengthen the cooperation between industry, academia and research, and promote the clinical translation and application of aging marker detection technology. Establishing a precise biological age clock through aging biomarkers will provide accurate measurements for predicting healthy lifespan, age-related diseases, and monitoring the effectiveness of aging interventions Wang Yanjiang said. Can a dual approach of disease prevention and health management intervene in aging? Cao Feng, chief physician of the Department of Cardiology of the Second Medical Center of the General Hospital of the Chinese People's Liberation Army, believes that some specific interventions can slow down or even reverse the "clock" of aging. Stem cell therapy, endogenous virus blockade, application of probiotics, and effective ingredients extracted from traditional Chinese medicine can contribute to anti-aging treatment to a certain extent. Cao Feng also introduced cutting-edge anti-aging strategies including injection of anti-aging vaccines and CAR-T therapy. Previous studies have shown that the application of anti-aging drugs, reasonable calorie restriction, balanced diet adjustments, and regular exercise can all slow down or even partially reverse the aging process to a certain extent Cao Feng explained that factors such as social environmental pressure and social deprivation may accelerate the aging process. Healthy aging not only requires prevention and treatment of major chronic diseases, but also cannot be ignored in daily health management. Cao Feng believes that the current focus of aging intervention is to prolong the healthy period and shorten the onset period. She advocates that people should take proactive actions from various aspects such as exercise, sleep, environment, and stress, and become their own health managers. At this meeting, experts reached a consensus on aging mechanisms and intervention research: to promote innovation and translational application of aging science research and prevention and control technologies; Transitioning from single disease treatment to systematic intervention for aging; Advance the timing of disease intervention to delay the decline of bodily functions; Prevent and treat age-related diseases to achieve healthy aging. Can the "centenarian medicine" delay the aging process of primates and humans? This long-standing problem that has plagued the scientific community has a new answer. Recently, the international academic journal Cell published a research achievement completed by Liu Guanghui, a researcher of the Institute of Zoology of the Chinese Academy of Sciences, and a cooperative team over eight years. This study, based on a primate model, confirms that long-term use of metformin can promote the rejuvenation of various tissues and organs in primates, reset the internal program of cellular aging, and thus delay the aging process. Metformin has been around for over 100 years and has been clinically used for over 60 years. However, in the past, this drug was only used for the treatment of type II diabetes, and its impact on the aging process of primates, including humans, has not been confirmed. This study adopted an interdisciplinary approach, integrating techniques such as physiological function assessment, medical imaging, multi parameter blood analysis, multi tissue pathological examination, and multidimensional omics, to conduct a systematic longitudinal study on middle-aged and elderly male crab eating monkeys who have been taking metformin for a long time. Research has confirmed that the drug has comprehensive anti-aging effects on 11 systems and 79 tissues and organs throughout the body of crab eating macaques, and can significantly enhance their cognitive abilities. Crab eating macaques have high similarities in physiological structure and function with humans, and are considered an ideal animal model for studying the aging process of humans Liu Guanghui introduced that the research team conducted a 40 month follow-up study on crab eating monkeys taking metformin. Through quantitative analysis of the thickness of the cerebral cortex, cognitive function, degree of periodontal bone degeneration, as well as the aging phenotype of multiple organ systems such as the liver, heart, lungs, small intestine, and skeletal muscle, it was found that metformin can systematically delay the aging of multiple tissues and organs in primates. With the help of computational biology analysis technology, Liu Guanghui's team, together with Zhang Weiqi's team, a researcher at the Chinese Academy of Sciences Beijing Institute of Genomics (National Bioinformatics Center), and Qu Jing's team, a researcher at the Institute of Zoology, Chinese Academy of Sciences, have constructed a multi-dimensional aging assessment model for primate tissues and organs using machine learning algorithms. This model can accurately quantify the systemic regulatory effects of metformin on aging. The research results indicate that in addition to traditional blood glucose and metabolic regulation functions, metformin can delay aging at the cellular level Zhang Weiqi introduced that there is a gene expression network mediated by the transcription factor Nrf2 within cells, and metformin can effectively activate the transcription factor Nrf2, enhancing the activity of cellular antioxidant capacity. We found that metformin can significantly reduce the biological age of primates Qu Jing explained that biological age is an indicator that comprehensively reflects the health status of the body. Researchers comprehensively evaluate biological age by integrating parameters from multiple levels such as molecules, cells, organs, and physiological functions. Research has found that crab eating monkeys taking metformin for a long time exhibit a "biological age reduction" effect, with a maximum age reduction of 6 years, which is roughly equivalent to 18 years on the human age scale. In addition, the results of high-precision single-cell level aging assessment show that metformin can effectively delay the aging of frontal lobe neurons in middle-aged and elderly monkeys, restore the structure and function of neurons. Meanwhile, metformin enhances the lipid metabolism and amino acid metabolism capacity of the liver, indicating its systematic and multi-target aging intervention effect. Aging is the biggest risk factor for chronic diseases, and the current paradigm of geriatric research is shifting from single chronic disease treatment to systematic intervention in the aging process Liu Guanghui introduced that the analysis of the mechanism by which metformin delays aging in this study not only provides a new perspective for understanding aging, but also offers a new path for preventing and treating age-related diseases. (New Society)