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With the deepening of population aging, the realization of "healthy aging" has become a major social and scientific problem that needs to be solved urgently in our country and even in the world. According to estimates, my country's elderly population aged 60 and above will exceed 400 million around 2035, accounting for more than 30% of the total population, entering a stage of severe aging.
Aging is the greatest risk factor for human chronic diseases, and the essence of chronic diseases in the elderly is the aging and degeneration of organs. Key scientific issues in the field of aging research mainly include:
(1) How old are we?
(2) Why do we get old?
(3) Can we age healthily?
Aging biomarkers are physiological and molecular indicators that indicate aging-related structural or functional degeneration at the body, organ, tissue, cell, and subcellular levels. They can be used to monitor and evaluate the biological changes associated with aging, and predict the evolution of organ aging to pathology It is helpful to answer the scientific question of "how old are we?" and is the basis and premise for in-depth assessment and early warning of aging, as well as intervention for aging and related diseases. Carrying out systematic research on aging markers has important theoretical significance for promoting the development of basic and translational medicine of aging, improving the health of the elderly population, and formulating a roadmap for "healthy aging" in China.
Recently, the English version of "Science China Life Sciences" (SCIENCE CHINA Life Sciences) published a "cover article" jointly written by more than 60 research groups of the Aging Biomarker Consortium (ABC). Review - "Biomarkers of aging".
This review refers to more than 2,000 research literatures in the field of aging. With over 90,000 words, 31 illustrations and 23 tables, it systematically summarizes the research on aging markers in cell aging, organ aging, aging clock and its application, and corresponding ethics. Important progress in the four aspects of social significance and social significance (Figure 1).
This review is the first to propose the basic attributes, dimensions and three "primary colors" (Primary colors, systemic, specificity and availability) of aging markers in the world, and defines six "pillars" of aging markers (Pillars, Physiological features, imaging features, histological features, cellular changes, molecular changes, and humoral secretion factors), and pointed out that "physiological behavioral features", "imaging features", and "humoral secretion factors" can be used as three factors for the clinical transformation of aging markers. available indicators.
This review is the most cutting-edge and detailed review of aging markers so far, which will help lead the development of aging assessment and early warning, and promote the formulation of "healthy aging" programs.
Figure 1 Overview of aging biomarkers
Biomarkers of Cellular Aging
Cells are the basic units that make up organs and organisms, and cell senescence is the driving force for the aging of organs and organisms. Biomarkers of cellular senescence can be used not only to monitor changes at the cellular level during aging, but also to indicate the biological age of an entire organ or organism. This section addresses epigenetic changes, genomic instability, telomere attrition, endosome disturbances, cell cycle arrest, mitochondrial dysfunction, imbalances in protein homeostasis, metabolic dysregulation, signaling pathway abnormalities, and aging-associated secretory phenotypes Ten aspects of cellular aging markers (Figure 2), clarified how the above markers reflect and even drive aging-related changes, and proposed that the discovery of new cellular aging markers can broaden people's understanding of aging mechanisms, so as to provide a basis for aging intervention provide potential targets.
Figure 2 Biomarkers of cellular senescence
Biomarkers of Organ Aging
The functional decline brought about by organ aging (usually manifested clinically as a variety of aging-related diseases) seriously affects the health and quality of life of the elderly population. In this part, from the six aspects of physiological characteristics, imaging characteristics, histological characteristics, cell changes, molecular changes and humoral secretion factors, it discusses in-depth research across 15 organs/systems (brain, heart, blood vessels, lungs, skeletal muscles, liver, Kidney, bone, fat, skin, intestine, pancreas, reproductive system, hematopoietic system and immune system) aging markers (Figure 3-4), provide an important reference for scientifically assessing the degree of organ aging and early warning of aging-related degenerative diseases .
Figure 3 Overview of organ/system aging markers
Figure 4 Biomarkers indicating the degree of aging in different organs
The Aging Clock and Its Applications
In addition to the cellular and organ levels, the individual and population levels also exhibit aging heterogeneity. Using composite metrics is helpful in assessing complex system aging, but picking the best combination is not an easy task. Based on large population cohorts, previous studies have identified biomarkers for aging measurement, combined with various modeling techniques such as artificial intelligence, and established multiple predictive models of biological age or aging clock. This part systematically introduces aging clocks and their applications, including phenotypic clocks, epigenomic clocks, transcriptome clocks, proteome clocks, metabolome clocks, rhythm clocks, longevity clocks, single-cell clocks, medical imaging clocks, composite clocks, And the application of artificial intelligence technology in the aging clock, and in-depth discussion of the problems and challenges faced by these models in clinical application (Figure 5).
Figure 5 Aging clock and its application
Ethical and social considerations in research on markers of aging
The field of biomarker research of aging is rapidly developing and shows great potential for preventing, diagnosing or treating diseases related to aging. However, the basic research and clinical translation of aging markers usually use animals and humans as subjects, and there are potential ethical, legal and social risks.
This part systematically discusses the ethical, legal and social risks related to the research of aging markers and their clinical transformation, and classifies them into four categories: (1) scientific value; (2) informed consent; (3) evaluation of disclosure of diagnostic results ; (4) Other issues. Establishing a normative ethical framework for research on aging markers will help provide guidance for researchers, clinicians, policy makers, and consumers, and ensure the long-term healthy development of the field of aging research.
Article source: China Science Life Sciences
Attached (corresponding author):
Liu Guanghui (Institute of Zoology, Chinese Academy of Sciences), Pei Gang (Tongji University), Zou Weiguo (Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences), Zhu Dahai (Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences), Zhao Yuzheng (East China University of Science and Technology), Zhao Tongbiao (Institute of Zoology, Chinese Academy of Sciences), Zhang Zhuohua (Xiangya Hospital, Central South University), Zhang Yunwu (Xiamen University School of Medicine), Zhang Yong (Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences), Zhang Weiqi (Beijing Institute of Genomics, Chinese Academy of Sciences), Zhang Liang ( Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences), Zhang Hongbo (Sun Yat-sen University), Zhang Cuntai (Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology), Yue Rui (Tongji University), Ye Jing (Shanghai Jiaotong University Ruijin Hospital), Xu Daichao (Chinese Academy of Sciences Shanghai Institute of Organic Chemistry), Xie Zhengwei (Peking University), Xiao Yichuan (Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences), Xiang Peng (Sun Yat-sen University), Huang Chaolan (Peking Union Medical College, Chinese Academy of Medical Sciences), Wang Yunfang(Changgung Hospital, Tsinghua University), Yanjiang Wang (Daping Hospital, Third Military Medical University), Xiaoning Wang (General Hospital of Chinese People’s Liberation Army), Xia Wang (Tsinghua University), Si Wang (Xuanwu Hospital, Capital Medical University), Shusen Wang (Nankai University), Tian Mei (Fudan University), Sun Yu (Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences), Sun Yi (Tongji University), Song Yangzhou (Sun Yat-sen University), Song Moshi (Institute of Zoology, Chinese Academy of Sciences), Ren Ruibao (Shanghai Jiaotong University) University Ruijin Hospital), Ren Jie (Beijing Institute of Genomics, Chinese Academy of Sciences), Qu Jing (Institute of Zoology, Chinese Academy of Sciences), Peng Yaojin (Institute of Zoology, Chinese Academy of Sciences), Nie Jing (Nanfang Hospital, Southern Medical University), Mao Zhiyong (Tongji University) , Ma Xinran (East China Normal University), Ma Shuai (Beijing Institute of Stem Cell and Regenerative Medicine), Luo Xianghang (Xiangya Hospital, Central South University), Liu Yong (Wuhan University), Liu Xingguo(Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences), Liu Qiang (Tianjin Medical University), Liu Qiang (University of Science and Technology of China), Liu Lin (Nankai University), Liu Feng (Central South University), Liu Baohua (Shenzhen University), Li Xin ( Institute of Zoology, Chinese Academy of Sciences), Li Jian (Beijing Institute of Geriatrics, Ministry of Health), Li Ji (Xiangya Hospital, Central South University), Kong Qingpeng (Kunming Institute of Zoology, Chinese Academy of Sciences), Ju Zhenyu (Jinan University), Huang Kai (Huazhong Science and Technology Union Hospital Affiliated to Tongji Medical College), Han Jingdong (Peking University), Gao Feng (Fourth Military Medical University), Ding Qiurong (Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences), Ding Yusen (Sichuan University), Ci Weimin (Beijing Genome Research Institute, Chinese Academy of Sciences) Institute), Chen Jun (Peking University), Chen Houzao (Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences), Chen Guobing (Jinan University), Chen Chang (Institute of Biophysics, Chinese Academy of Sciences), Chen Biao(Xuanwu Hospital of Capital Medical University), Cao Zhongwei (Sichuan University), Cao Feng (General Hospital of the Chinese People's Liberation Army)
Original link:
A heavy review of "markers of aging": cellular aging, organ aging, aging clock and its application