This strategic proposal aims to elucidate the mechanisms of transformation and disruption of biological resilience with aging, and to create health and medical modalities (e.g., pharmaceuticals) for predictive/preventive diagnosis and treatment of age-related diseases.

The extension of healthy life expectancy is an important direction that can not only improve people's QOL but also solve problems such as the decline in the working population and the increase in social security costs. Age-related diseases are the main factor that hinders the extension of healthy life expectancy, and the rapid increase in age-related diseases expected to accompany the rapid aging of the population has become a major problem both in Japan and overseas.

In considering health and medical technologies for age-related diseases, it is important to take a prognostic/preventive approach from three perspectives: health promotion, prevention of severe disease (including prevention of onset), and prevention of serious attacks and recurrence. Conventional life science and clinical medicine research has focused on the research and development of diagnostic and therapeutic methods for individual age-related diseases at the stage where symptoms have already progressed. This strategic proposal will focus on the mechanisms of alteration and disruption of biological resilience during aging and will elucidate the mechanisms of onset of age-related diseases and the common principles underlying multiple age-related diseases by deepening our understanding of the nature of aging. By doing so, we aim to create the seeds for predictive and preventive diagnostic technologies and therapeutic modalities for age-related diseases.

The first important R&D task is the development and advancement of advanced measurement and data analysis technologies that are necessary for clarifying the complex molecular and cellular networks that underlie the research targets of this strategic proposal. By utilizing these advanced measurement and data analysis technologies, we will elucidate the relationship between various life phenomena and aging, and also elucidate the enormous diversity and individual differences observed in aging from the cellular level to the individual level through model organism research. Based on the findings obtained through these studies, we will deepen our understanding of the mechanisms of aging and age-related diseases and search for ways to control them. Through the search for biomarkers associated with aging and their integrated validation, we will establish an evaluation index for the "human aging progression" and promote clinical development of predictive/preventive diagnostic and therapeutic seeds for which sufficient scientific evidence has been accumulated. Specifically, research and development will be promoted in the following four pillars.

• Pillar 1: Advanced measurement and data analysis technologies to accelerate aging research

  Single cell omics, non-targeted analysis, multi-omics, imaging, spatio-temporal omics, and new technology concepts leading to measurement and analysis of a wide range, deep, and long-term time series.

• Pillar 2: Basic life science research on aging

  Diverse life phenomena (nutrition/metabolism, inflammation, biological clock, quality control mechanisms (nucleic acids/molecules/cells, etc.), cell-to-cell diversity, individual differences, model organisms, non-model organisms showing characteristic aging-related phenotypes, mathematical models/simulations/AI)

• Pillar 3: Aging-related disease research based on understanding of aging

  Search for and precise classification of aging-related cells (groups) and molecules (groups), multi-organ networks (whole-body networks of nerves/signaling molecules), relationship between mind and body, aging-related disease research based on understanding of aging in aging, aging-related biomarkers in aging, human large-scale data infrastructure (state-of-the-art data analysis methods: AI, machine learning, etc.)

• Pillar 4: Clinical development of predictive/preventive diagnostic technologies and therapeutic modalities

  Clinical development of predictive/preventive diagnostic technologies and therapeutic modalities for aging-related diseases, and multifaceted value evaluation of clinical development seeds (impact on individuals and society)

Establish a virtual-type research institute and promote research under the strong leadership of the institute director. Design a portfolio that continues to generate results in the short to long term by adopting a balanced mix of basic research themes and exit-oriented themes. In addition to the steady achievement of the initial research plan, unexpected results will be highly valued, and flexible allocation of research funds will be implemented.

In the Virtual Research Institute, the research environment will be improved (promotion of a good balance between development and support of advanced measurement and data analysis technologies, development of a bioresource support infrastructure), and the environment will be improved for multidisciplinary fusion and human resource development (acceleration of interdisciplinary research, acceleration of human data science research, acceleration of collaboration with the humanities and social sciences, consideration of ELSI/ RRI, human resource development in parallel with interdisciplinary research), and improve the environment for clinical development (industry-academia collaboration, regulatory science for predictive/preventive diagnostic technologies and therapeutic modalities).

As social and economic ripple effects, the project is expected to contribute to the extension of healthy life expectancy through the realization of predictive/preventive diagnosis and treatment of age-related diseases, to the revitalization of health and medical-related industries (pharmaceuticals, healthcare, insurance, etc.), and to the optimization of medical and nursing care costs. As for scientific and technological ripple effects, the following are expected: raising the level of the entire field of life science and clinical medicine by strengthening advanced measurement and data analysis technologies, strengthening and integrating the element-reduction approach and the data-driven approach, accelerating research on human subjects, and establishing new academic fields through the fusion of multiple fields.