noitcnuFfossoLMeAcAcTo understand how organisms determine “time” and to develop methods to measure and intervene in aging.11111111009988223344775566Diverse agingDiseaseof FrailtyEndowed Research ProjectDivision of Molecular Biology of AgingDirectorAssociate Professor,Research Institute for Science and TechnologyMotoshi HayanoPh.D. We aim to decipher the biology of “time” beyond humans—through cross-disciplinary research on aging and species diversity—while developing impactful diagnostics, therapeutics, and services for global deployment.Tokyo University of ScienceTokyo University of Science BackgroundandObjectivesoftheResearchDivisionResearchTopicshave established a novel mouse model, ICE (Inducible Changes to the Epigenome), for studying epigenomic control of aging (Hayano * and Yang * et al., Cell 2023; Yang et al., Cell 2024; Kato et al., Dev. Cell 2021). This project aims to elucidate when and how aging is initiated, as well as the pace of aging (see figure). 2. Objective Measurement of Aging Biological aging clocks, which provide objective indicators of functional aging distinct from chronological age, are becoming increasingly refined. These clocks primarily use DNA methylation but are expanding to include biomarkers such as circulating peptides, gut microbiota, speech, and movement data. In this study, we aim to establish objective aging metrics by comparing samples from mice, humans, and various species. In addition to epigenomic data, we will incorporate physical properties such as tissue viscoelasticity. For human studies, we will integrate medical and healthcare data with surrogate models, longitudinal learning, and personalized health digital twins (see figure). 3. Molecular Understanding of Aging across Diverse Species We will investigate molecular mechanisms of aging across a wide range of species — from the Greenland shark, known to live over 400 years, to short-lived species such as ayu (sweetfish) and giant squids. We will also study jellyfish that undergo repeated self-renewal through parthenogenesis, penguins with unique gut microbiota, and other organisms exhibiting unique temporal dynamics. These investigations aim to uncover the molecular underpinnings of time-related biological change across evolutionary contexts (see figure). 4. Development of Interventions Targeting the Reversibility of Aging We define aging as the progressive loss of function and homeostasis in cells and organs over time. This project aims to develop therapeutic strategies targeting the molecular mechanisms underlying aging-related decline. Our approaches include the development of medical devices based on non-visual photoreceptor OPN5 using non-invasive 380 nm light, epigenomic interventions for conditions such as sarcopenia and dementia through drug or functional food development, and ex vivo genome editing for therapeutic applications. These technologies will be advanced in collaboration with startups and industry partners to promote societal implementation (see figure).Aging Clock1122ThresholdEpigenome changesDevelopment of diagnostic and intervention methods based on molecular understandingMeAccelerated aging via the epigenome and reversibilityWe will analyze aging across species using molecular biology, physics, and AI, and promote social implementation including startups.ObjectivesAnalysis of aging as a mechanism for temporal regulation in organisms.Regulation of aging through epigenomeDNA damage, infection, metabolismFuture Development Goals Aging is a physiological change in cells and organs over time and is known to be a major risk factor for various diseases in humans. However, in other species — such as turtles or jellyfish — aging does not necessarily lead to functional decline or disease. Even within a single organism, some cells age more readily, while others exhibit enhanced robustness. From a biological standpoint, analyzing the responses and aging phenomena that occur in diverse organisms in response to both internal and external environmental conditions is essential for understanding the meaning and function of “time” in biology. At the cellular level, the inability to maintain function over time leads to a breakdown of homeostasis in the organism as a whole, which we refer to as “disease.” When the condition lacks a specific diagnosis, we use general terms such as “age-related organ dysfunction,” “frailty,” or “aging.” However, at the cellular level, disease and aging are not fundamentally different. Based on the idea that aging is treatable by improving biological function, innovation focused on predicting and extending healthspan is gaining momentum, along with corresponding investment and business development. In addition, as concepts like hedonic and eudaimonic well-being suggest, it is equally important to understand and sustain “happiness” alongside functional aging in humans. With this in mind, our division aims to uncover the diversity of aging through the lens of the biology of time, while simultaneously creating innovation and social impact that maximize the value of healthspan and well-being in humans.1. Regulation of Aging through the Epigenome The epigenome refers to mechanisms that regulate gene expression quantitatively and qualitatively in an acquired manner, and it plays a crucial role in directing stem cells to differentiate into specific cell types such as neurons or hepatocytes. Recently, the concept of “epigenomic memory” has emerged, highlighting how environmental factors such as diet and exercise can leave molecular “marks” distinct from DNA sequences, which are retained over time and influence gene expression and cellular function. We Established: April, 2025 mhayano@rs.tus.ac.jpATM/ATRAcGene expressionLoss of epigenetic identity3636
元のページ ../index.html#35