[Aging] Fundamental Understanding of Age-Related Organismal Transformations

Strategic Objective

Elucidation of the mechanisms relating to changes in biological robustness associated with aging and control of age-related diseases

Program Supervisor

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Naoki Mochizuki (Director/Research Institute Director, National Cerebral and Cardiovascular Center)

Research Supervisor

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Masayuki Miura (Professor, Graduate School of Pharmaceutical Sciences, Faculty of Pharmaceutical Science, The University of Tokyo)

Overview

 This research area aims for elucidation of the mechanisms relating to changes in biological robustness associated with aging and control of age-related diseases. To achieve the Strategic Objective set by the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan Science and Technology Agency (JST) and Japan Agency for Medical Research and Development (AMED) have simultaneously established research areas under three different funding programs (PRESTO, AMED-CREST, and PRIME) and promote research while collaborating with each other under the initiative of Program Supervisor (PS) who is in charge of collaboration among these three programs. Please note that JST may share research proposals with AMED during the selection process.

Policy of Program Supervisor


 Aging is inseparable from longevity. Organisms have biological robustness that is supported by resilience mechanisms, the ability to adapt to the environment and external stimuli, to complete their natural life. Therefore, we consider that aging could be correlated well with alteration of robustness and resilience of organisms. It is, therefore, important to promote research in order to elucidate the aging mechanism and controlling age-related diseases that are associated with life extension, by investigating the mechanism of alteration using new technologies and analytical methods. The recent advancement of analytical measurement and technologies for components that are the basis of life phenomena, such as molecules, cells, tissues, and organs making up living organisms has been remarkable. These research methods contribute to the dramatically advancing the elucidation of the mechanisms of aging. To explore the fundamental principles of aging, using these cutting-edge technologies and to elucidate the preventive/therapeutic mechanisms of age-related diseases based on these principles, the establishment of an integrated research network among researchers of the basic research and the development of research proposals for prevention and treatment, and promotion of research in a comprehensive way are expected. We tackle the basic understanding of aging by utilizing advanced analysis technologies in the human, model organisms and the organisms that show characteristic aging phenomena. For this purpose, collaboration with researchers of aging research and the sharing of technology are essential. We thrive to make this research area where active joint investigation between researchers and exchange of samples are possible so that we can discover the universal principle among organisms.
 In addition, JST and AMED manage the research areas under PRESTO, AMED-CREST, and PRIME jointly for realization of the goals, promote integrated understanding of aging research by integrating and aligning multifaceted knowledge and technologies from different fields in research promoted respectively, and address original research and development ahead of other countries. Moreover, we are planning to collaborate with Moonshot Research and Development Program (from the 2020 academic year to the 2029 academic year) Goal #7 “Realization of sustainable care systems to overcome major diseases by 2040, for enjoying one’s life with relief and release from health concerns until 100 years old.”

Policy of Research Supervisor


 As aging is recognized as a social problem globally, aging has been regarded as a drug discovery target and attention is focused on research proposals, such as searching for anti-aging drugs. However, the history of aging research is still short, and it cannot be said that basic knowledge of aging, a life phenomenon, has been sufficiently understood. Here, defining aging as “transformation of robustness and resilience of organisms over time”, this research area aims for basic understanding of the transformation of biological robustness and resilience with aging using a wide range of bioscientific approaches.
 Biological robustness and resilience are constantly transforming in the body from embryonic development, growth, and aging until death. Organismal transformations described here refers to the continuous changes with biological processes in living organisms, which includes epigenetic gene expression control, metabolism, redox, intracellular signal transduction, and other factors at the molecular level, and differentiation, proliferation, maintenance and dormancy of stem cells, cell senescence, cell degeneration and cell death at the cellular level. At the tissue level, this includes temporal changes in various tissues in the body, such as immune, nervus and endocrine system, tissue damage, repair, and cancer development. In addition, it is important to know how biological robustness and resilience has developed in the process of evolution and how organismal aging has been defined.
 In order to understand these age-related organismal transformations, every effort should be made, utilizing all measurement and analysis technologies that have been developed in life and medical research, such as multi-omics and imaging, data analysis, simulation, and genome editing technologies. Besides model organisms (mouse, fish, Drosophila, nematodes, yeast, and others) that have been used so far, development of novel model organisms of short-lived or long-lived species, and of organoids will be included as a research theme of this research area.

Research Area Advisors

Makoto Arita Professor, Faculty of Pharmacy, Keio University
Hiroshi Kimura Professor, Institute of Innovation Research, Tokyo Institute of Technology
Shigeki Kiyonaka Professor, Graduate School of Engineering, Nagoya University
Takehiko Kobayashi Professor, Institute for Quantitative Biosciences, The University of Tokyo
Nobuyuki Takakura Professor, Research Institute for Microbial Diseases, Osaka University
Chikashi Terao Team Leader, Center for Integrative Medical Sciences, RIKEN
Fumiko Toyoshima Professor, Institute for Life and Medical Sciences, Kyoto University
Hiroshi Nakajima Professor, Graduate School of Medicine, Chiba University
Eiji Hara Professor, Research Institute for Microbial Diseases, Osaka University
Kunihiro Matsumoto Professor Emeritus, Graduate School of Science, Nagoya University

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