Research Centers

Pursuing the mechanisms of aging and developing new therapeutic strategies

The Research Institute for Diseases of Old Age was established in 1999 with the mission to elucidate the mechanisms underlying geriatric disorders and to develop novel therapeutic approaches. Over the past 25 years, the Center has produced numerous internationally recognized achievements aimed at unraveling the mysteries of aging—an enigma that still remains largely unsolved—and linking these discoveries to disease prevention and treatment.

Currently, our research focuses primarily on neurodegenerative and age-associated diseases. Led by departments in neuroscience, physiology, neurology, psychiatry, and neurosurgery, as well as respiratory and cardiovascular medicine, we are advancing three major research programs:　

　　Pathogenesis and protective mechanisms in Parkinson’s disease and related disorders

　　Pathogenesis and protective mechanisms in dementia and related neurodegenerative diseases

　　Neural mechanisms and functional restoration of higher brain functions

These projects are supported by a robust infrastructure and highly specialized core research groups. By centralizing advanced imaging equipment—such as confocal laser and super-resolution microscopes—and shared laboratory facilities, we have established an environment that enables analyses ranging from the super-resolution light microscopy level to high-resolution electron microscopy. Our basic science teams also drive technological innovation, having developed unique electron microscopy methods, including correlative light–electron microscopy (CLEM) and freeze-fracture replica techniques for protein localization at the nanoscale level.

In 2002, the Center completed a 200 m² SPF (specific pathogen–free) animal facility capable of housing 6,872 model animals, equipped with P2-level laboratories, sterilization and cleaning rooms, and storage areas. This facility allows research that seamlessly bridges the genetic and cellular levels with animal and human studies.

Establishing an advanced imaging platform for understanding brain function and structure

Juntendo University hosts multiple internationally leading research groups in brain science and clinical neurology. Building upon this strength, our Center spearheaded the MEXT “Private University Research Branding Project” (2016–2019) titled “Visualizing Brain Function and Structure: Establishing a Multidimensional Imaging Center.”

The project brought together an interdisciplinary network of researchers—including clinical specialists (neurology, neurosurgery, psychiatry, radiology), basic scientists (physiology, morphology, regenerative medicine), and laboratories from the Graduate School of Health and Sports Science working on the “Healthy Brain Project.” This collaboration established an advanced and integrative platform for neuroscience research.

To “visualize brain function and structure,” we aimed to develop imaging techniques capable of comprehensive analyses from the cellular to the whole-organism level. Through integration of macro-scale (human patients, healthy individuals, top athletes, animal models) and micro-scale (cellular) imaging, the Center established a multidimensional imaging hub for high-precision neural circuit analysis.

Juntendo’s extensive resources enabled seamless analyses from macro to micro scales across human brains (patients–healthy individuals–athletes), animal brains (disease models including aging–controls–high-performance models), and various neural cell systems (patient-derived iPSCs–healthy iPSCs–athlete iPSCs). This integrated system facilitates the identification of novel biomarkers relevant to psychiatric and neurological diseases.

Detecting abnormal protein aggregates in serum: toward early diagnosis and disease mechanism discovery

Among the Center’s latest breakthroughs is a major advance toward treating previously intractable age-related diseases. Professor Nobutaka Hattori and his neurology group have succeeded in establishing a serum-based diagnostic method for synucleinopathies, including Parkinson’s disease.

Synucleinopathies are neurodegenerative disorders characterized by the abnormal aggregation of α-synuclein in the brain and peripheral tissues, leading to neuronal loss and progressive symptoms such as tremor, bradykinesia, dementia, and autonomic dysfunction. Currently, there is no curative therapy.

The research team hypothesized that blood may play a key role in the systemic spread of pathology. They successfully detected pathogenic α-synuclein aggregates—termed α-synuclein “seeds”—in the serum of patients. Remarkably, they discovered for the first time that the structural and biochemical properties of these seeds differ among diseases, suggesting that distinct seed types could serve as diagnostic markers for differentiating synucleinopathies.

This groundbreaking work not only provides a basis for blood-based diagnosis of neurodegenerative diseases but also opens new avenues for understanding disease mechanisms and developing targeted therapies.

Developing vaccines that eliminate senescent cells causing age-related diseases

Another significant line of research is the development of senolytic vaccines—vaccines designed to eliminate senescent cells—led by Professor Toru Minamino and his cardiology group, pioneers in the biology of aging for over two decades.

Senescent cells, which arise from chromosomal damage due to metabolic stress (aging, obesity, etc.), lose their ability to divide but persist in tissues, releasing inflammatory factors that promote chronic inflammation and the onset of age-related diseases such as Alzheimer’s disease and metabolic syndrome.

The group identified proteins specifically expressed on senescent cells in mice, serving as “senescence antigens.” By developing a vaccine targeting these antigens, they succeeded in selectively eliminating senescent cells. Administration of this vaccine improved glucose metabolism, reduced atherosclerosis, and even extended the lifespan of progeroid mice. These findings highlight the potential of targeting disease-specific senescence antigens for tailored therapeutic strategies.

Fostering young researchers and building a sustainable research environment for healthy aging

Japan’s population is aging rapidly, with an average life expectancy of 84.6 years (87.6 for women, 81.5 for men). Today, 29.1% of the population is aged 65 or older, and 14.9% is 75 or older. Yet, the fundamental question “What is aging?” remains unanswered. Our Center’s mission is to elucidate the biological essence of aging, clarify its link to disease, and develop therapeutic strategies based on this understanding.

To achieve this, it is crucial not to confine our research within the university but to engage and support young scientists both within and beyond Juntendo. We aim to establish the Center as Japan’s leading hub for comprehensive research on the pathophysiology, treatment, and care of geriatric diseases.

Our current staff conduct studies on neuroscience, cell biology (including lipid droplet biology), and lysosomal/autophagic dysfunction in neurodegenerative diseases—so-called “storage disorders” caused by defective degradation of cellular metabolites. We are also advancing light and electron microscopy–based localization studies of brain molecules and promoting collaborative and interdisciplinary research through the development of new imaging methodologies.

To strengthen collaborative research, we are planning the establishment of shared laboratories and instrumentation facilities that will be accessible to researchers studying aging and age-related diseases. In addition to maintaining state-of-the-art electron microscopes and imaging technologies, we are expanding basic research equipment and technical support staff to foster a more open and dynamic research environment.

We believe that the Center’s role will become increasingly important in the coming years. Enhancing our research capacity is essential to realize a society where people can age healthily and live long, fulfilling lives.