IARO 2024
THE 2ND
INTERNATIONALSYMPOSIUM

June 19, 2024

https://www.iaro.link/

The 2nd International Symposium of International Anti-aging
and Regenerative Medicine Organization (IARO)
June 19, 2024 (Wed)
Ito International Research Center B2F, The University of Tokyo

Welcome Message
Dear Participants,
Welcome to the "IARO 2024 The 2nd International Symposium." As the Chairmanof the International Anti-aging and Regenerative Medicine Organization (IARO), it is
my great honor to host this significant event. Today, we bring together distinguishedresearchers at the forefront of regenerative medicine and anti-aging therapy to discuss thelatest advancements and innovative technologies.
Our goal is to develop new treatments that extend healthy lifespans and improve thequality of life. In today's program, experts from various fields will share valuable insights
and explore new possibilities for the future of medicine.
I hope this symposium proves to be a meaningful and rewarding experience for all of you.

Sincerely,
Dr. Tatsuya Yamasoba
Chairman of IARO / Director of Tokyo Teishin Hospital /Professor Emeritus of the University of Tokyo

PROGRAM
11:00

Opening Ceremony and Greetings
Dr Tatsuya Yamasoba
Chairman of IARO / Director of Tokyo Teishin Hospital / Professor Emeritus of the University of Tokyo

Dr Somarch Wongkhomthong
Former CEO of Bangkok Dusit Medical Services (BDMS)
Seminar, 25 minutes including Q&A

11:20-11:45

Aquatic Animal Stem Cells Hold the Future of Regenerative
Medicine
Chee-Wee LEE, Ph.D.

11:45-12:10

Advances in Exosomes, Senolytics, Heart and Kidney Treatments
Kampon Sriwatanakul, M.D., Ph.D.

12:10-12:35

Approach to the Next-Generation Cell Processing Facility That is
Energy-Saving, Labor-Saving, and Highly Productive, Achieved by
Non-Woven Fabric Automatic Culture System
Shunmei Chiba, M.D., Ph.D.

12:35-13:35

Lunch

13:35-14:00

Decidualization and Angio-myogenesis Potentials of Placental
Choriodecidual Membrane-Derived MSCs
Thai-Yen Ling, Ph.D.

Stem Cell and Its Derivatives in Aging Disease Treatment
Rita Yen-Hua Huang, Ph.D.
14:00-14:25

Uncovering the Relationship Between Aging and Cancer Passenger
Mutations Through Liquid Biopsy
Tomohiro Umezu, Ph.D.

14:25-14:50

The New IARO Laboratory at Mahidol University
Pongrama Ramasoota, DVM, Ph.D.

～Short break 15min～
15:05-15:30

The Future of Medicine iPSC Technology Will Usher In
Koji Tanabe, Ph.D.

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15:30-15:55

Immunotherapy for Cancer Using iNKT Cell and Next Generation
NKT Therapy With Drug Delivery System
Taehun Hong, Ph.D.

15:55-16:20

Problems of Speech and Swallowing in Human Beings, theAdditional Solutions with Regeneration, Instead of Just Anti-Aging
Koichi Tsunoda, M.D., Ph.D.

Aging of the Olfactory System: Pathophysiology and Treatment
Strategies
Kenji Kondo, M.D., Ph.D.
16:20-16:45

Ultra-Low Dose Computed Tomography Combined with Artificial
Intelligence for Enhanced Health Screening: A Nexus of Evidence,
Innovation and Integrative Medicine
Richard H. Kaszynski, M.D., Ph.D.

Network: iirc-hall
Password: #09-20-guest

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Aquatic Animal Stem Cells Hold the Future of Regenerative
Medicine
Chee-Wee LEE, Ph.D.
Principal Scientist & Technology Advisor- Temasek Polytechnic, Singapore
Co-Director- Centre for Aquaculture, Innovation & Education, Nanyang Technological University, Singapore
Associate Professor- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Associate Professor- School of Chemistry, Chemical Engineering & Biotechnology, College of Engineering, Nanyang Technological
University, Singapore

Aquatic organisms, sculpted by millions of years of evolutionary pressure, possess a remarkable capacity for regeneration,
often surpassing that of their terrestrial counterparts. Their unique adaptations, including scarless healing and diverse stem
cell populations, offer a treasure trove of potential for regenerative medicine. This presentation explores two groundbreaking
applications of marine-derived biomaterials that leverage this innate regenerative prowess.
Firstly, we delve into the use of coral-derived biomaterials as bone graft substitutes. Their porous structure, similar
in composition to human bone, provides an ideal scaffold for bone tissue integration and growth. Moreover, theirbiocompatibility minimizes adverse immune responses, a common challenge with traditional bone grafts. This approachpromises to enhance bone regeneration, reduce complications, and provide a sustainable source of biomaterial for
orthopaedic procedures.
Secondly, we examine the burgeoning field of aquatic animal stem cell research and its implications for tissue engineering.
Derived from sources as diverse as fish skin, marine sponges, sea cucumbers, and axolotls, these stem cells possess remarkable
plasticity, capable of differentiating into various cell types. Their rapid proliferation and inherent resilience to environmental
stressors make them ideal candidates for regenerative therapies with lower production costs. Results with tilapia spleenderived mesenchymal cells will be presented. By combining these potent stem cells with coral scaffolds, researchers aredeveloping innovative solutions for complex tissue reconstruction, including advanced skin grafts, with the potential torevolutionize wound care and burn treatment.
Beyond these specific applications, aquatic-derived biomaterials offer several advantages over traditional mammalian sources.
Their enhanced biosecurity reduces the risk of disease transmission, while their ethical sourcing circumvents the controversies
associated with embryonic stem cells. Additionally, the evolutionary distance between aquatic animals and humans may leadto reduced immunogenicity and a lower risk of rejection in transplantation.
While the potential of aquatic-derived biomaterials is vast, translating these advancements into clinical practice requires
addressing challenges in production and standardization. These include optimizing isolation and culture techniques,
ensuring consistent quality control, and scaling up production to meet clinical demands. Nevertheless, ongoing research anddevelopment in this field promise to unlock the full potential of marine-derived biomaterials, paving the way for a new era ofregenerative medicine that harnesses the power of the ocean to heal and restore human tissues.

4Advances in Exosomes, Senolytics, Heart and Kidney Treatments
Kampon Sriwatanakul, M.D., Ph.D.
Chairman- National Health Charter of Thailand
General Manager- Wellness Group, Royal Thai Wellness Association
Chairperson- Thailand Wellness Tourism Network
Advisor- Thai Association for Anti-Aging and Regenerative Medicine

We are entering an evolution in cellular medicine. As these bio pharmaceuticals are becoming more understood, thetreatment applications continue to advance and improve.
Exosomes are Nano-sized vesicles, containing biomolecules that are secreted by virtually every cell type in the body. In cellbiology, a vesicle is a self-contained structure consisting of fluid enclosed by an outer membrane called the lipid bilayer.
Basically, an exosome is a vesicle which is like a tiny bubble that stores, and transports materials, protein, DNA, and RNAof the cells that secrete them. Growing evidences indicate that many of the observed therapeutic outcomes of stem cell-based
therapy are due to paracrine effects rather than long-term engraftment and survival of transplanted cells. Given their ability
to cross biological barriers and mediate intercellular information transfer of bioactive molecules, extracellular vesicles or
exosomes are being explored as potential cell-free therapeutic agents.
Senolytics are a relatively new class of treatments that focuses on the removal of senescent cells. Senescent stem cells comprisea small number of total cells in the body, but they secrete pro-inflammatory cytokines, chemokines, and extracellularmatrix proteases, which together form the senescence-associated secretory phenotype or SASP. The resulting SASP is thought tosignificantly contribute to aging and cancer and thus Senolytics and removal of SASP is a potential strategy for promoting
health and longevity.
Senolytic cell therapy is a new therapy that aims in physically removing these senescent stem and somatic cells from the bloodstream without the use of drugs
Natural Killer T (NKT) cells are a subset of T cells that have both innate and adaptive immune functions. They recognize
glycolipid antigens presented by the CD1d molecule on antigen-presenting cells. The idea of using NKT cells for senescentcell therapy revolves around their ability to recognize and eliminate abnormal or aged cells. By targeting senescent cells, NKT
cells could potentially help mitigate age-related inflammation and tissue dysfunction, thereby promoting healthy aging.
Traditional treatments for Cardiovascular Disease and Chronic Kidney Disease often struggle to significantly enhance a patient’s
quality of life. For those suffering from Cardiovascular Disease, conventional approaches involve long-term medication use
to manage symptoms and underlying causes, as well as surgical interventions such as bypass surgery or angioplasty. Kidney
patients typically have fewer treatment options compared to heart patients.
We are offering an integrative medical alternative to traditional medication and surgical approaches. In a hospital catheter
lab, patients can receive specialized stem cells delivered directly to the heart and both kidneys. This innovative treatment has
successfully benefited hundreds of patients, offering hope for those seeking a less invasive and more effective solution.

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Approach to the Next-Generation Cell Processing Facility That is
Energy-Saving, Labor-Saving, and Highly Productive, Achievedby Non-Woven Fabric Automatic Culture System
Shunmei Chiba M.D., Ph.D.
CEO- FullStem Co., Ltd.
Member of the Clinical Cultivator System Committee- The Japanese Society for Regenerative Medicine

Ahead of other countries, Japan has been implementing regenerative medicine under the Law for Ensuring the Safety ofRegenerative Medicine. In this environment, central kitchen-type contract cell processing facilities have made it possible formany clinics to provide regenerative medicine widely. However, in cell processing facilities using the conventional manuallabor method, if high productivity is desired, a large facility and space that can accommodate a large number of workers anda large number of culture equipment are required. In order to maintain the production environment, the cleanliness of the
air must be maintained at all times, and the larger the space, the higher the electricity and running costs for appropriate air
condition, leading to a negative spiral. The largest source of contamination in cell processing is humans, and since there is aphysical limit to the amount of manual labor, there is no qualitative or quantitative development potential for cells in a large
facility with many labors.
Naturally, the first step is expected to be to achieve high productivity through the use of automated culture system, and massculture techniques and devices developed for the production of vaccines and antibodies will be introduced. In reality, they
are not suitable for stem cell culture and are not commercially available device with high practicality in terms of quality andquantity.
We are the only company in the world that possesses automated culture technology utilizing non-woven fabric as a scaffold
for stem cells, and similar technology itself does not exist because cells cultured on non-woven fabric cannot be peeled
off by others. Nonwoven fabrics have the largest culture area of all cell scaffold materials, which enables space-saving andhigh-density culture that cannot be achieved with other scaffold materials and culture techniques. The three-dimensional
environment composed of intricate fibers creates an environment close to nature, as if the cells existed in vivo, and the cellaging phenomenon of hypertrophy in culture is suppressed.
We would like to report on the application of this non-woven automated cell culture system to next-generation cellprocessing facilities, while explaining the cell processing technology using this system.

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Decidualization and Angio-myogenesis Potentials of Placental
Choriodecidual Membrane-Derived MSCs
Thai-Yen Ling, Ph.D.
Associate Professor and Director- Department and Graduate Institute of Pharmacology College of Medicine, National Taiwan University

Our studies demonstrated a distinctive type of MSCs derived from the placental choriodecidual membrane, termed pcMSCs,
characterized by the expression of estrogen receptor (ER) and progesterone receptor (PR). In vitro studies revealed that
pcMSCs exhibit remarkable decidualization potential when stimulated by estrogen/progesterone or agents such as cAMP/
Medroxyprogesterone 17-acetate (MPA), resulting in the secretion of decidualization biomarkers, including prolactin (PRL)
and insulin-like growth factor-binding protein-1 (IGFBP-1). Furthermore, pcMSCs demonstrate pro-angiogenic and muscle
regeneration properties, showing therapeutic effects in a critical limb ischemia (CLI) mouse model. Treatment with pcMSCs
led to improved blood perfusion, reversal of muscle atrophy, and fibrosis within two weeks. Muscle repair was evident
through satellite cell activation and enhanced protein expression in the muscle regeneration pathway post pcMSCs treatment.
Taken altogether, these findings show the decidualization and angio-myogenesis potentials of pcMSCs for application inclinical use.

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Stem Cell and Its Derivatives in Aging Disease Treatment
Rita Yen-Hua Huang, Ph.D.
Distinguished Professor- Department of Biochemistry and Molecular Cell Biology, International PhD Program in Cell Therapy andRegenerative Medicine, College of Medicine, Taipei Medical University

The utilization of stem cells and their derivatives in the treatment of aging-related diseases represents a promising frontier inadvanced cell and gene therapy (CGT). Stem cells, including induced pluripotent stem cells (iPSCs) and mesenchymal stem
cells (MSCs), possess the remarkable ability to differentiate into diverse cell types or secrete beneficial derivatives (secretome
or exosome), providing potential solutions for age-related degenerative conditions. Furthermore, the systematic safety of
CGT in clinical applications is garnering increased attention. This speech delves into the therapeutic potential of stem
cells and their derivatives in addressing systemic safety and aging-related diseases, with a specific focus on the treatment ofinfertility-related premature ovarian insufficiency (POI) and its associated circadian rhythm disorder.

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Uncovering the Relationship Between Aging and Cancer
Passenger Mutations Through Liquid Biopsy
Tomohiro Umezu, Ph.D.
Associate Professor- Department of Molecular Pathology, Tokyo Medical University
Co-author:

Masahiko Kuroda
Senior Professor-Department of Molecular Pathology, Tokyo Medical University

Organisms age due to internal factors such as aging and stress, as well as external factors like ultraviolet radiation andchemicals. Advances in science have elucidated the molecular mechanisms of this aging process, and the definition of aging
has become increasingly clear. Recently, senolytic drugs targeting senescent cells that accumulate in the body with age havealso been introduced. However, there are still many unknowns regarding the relationship between "aging necessary for
maintaining homeostasis" and "aging that causes diseases," and understanding these relationships is essential for the practicalapplication of anti-aging treatments.
Furthermore, it is known that aging and cancer are closely related, and the accumulation of genomic mutations with aging
has been confirmed to increase the risk of cancer development. This is a significant social issue, especially in Japan, where theaging population is rapidly growing. In this context, we aim to elucidate the involvement of "genomic damage" accumulated
due to aging in the development of cancer.
With the spread of NGS and gene analysis technologies, cancer genomic medicine has significantly advanced, and cancer
panel testing is now conducted within insurance coverage. Genomic analysis from cancer tissue as well as liquid biopsy
panel diagnostics have become practical. Since determining driver genes that serve as molecular targets for cancer treatment
is crucial, mutation analysis of driver genes, which are directly involved in cancer development and proliferation, has been
the focus. However, recent findings have shown that not only driver genes but also mutations in passenger genes and noncoding regions are important in tumor development. Passenger mutations, reflecting the genetic diversity acquired during
the evolution of cancer cells, provide crucial information about cancer progression.
In this study, we investigated the biological significance of genomic damage, including passenger mutations accumulatedwith aging, with the aim of applying this knowledge to next-generation cancer diagnosis, prognosis monitoring systems,
and novel targeted therapies. From the perspective of early cancer diagnosis, we attempted to detect these mutations fromcirculating cell-free DNA (cfDNA) in the blood. To comprehensively analyze passenger mutations scattered throughout the
genome, we have also developed a signature analysis for these mutations. In this symposium, we will introduce our analysis
pipeline for detecting genomic mutations from plasma cfDNA and present the latest data.

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The New IARO Laboratory at Mahidol University
Pongrama Ramasoota, DVM, Ph.D.
Director- Center of Excellent for Antibody Research (CEAR), Faculty of Tropical Medicine, Mahidol University

After the MOU between Dean of Faculty of Tropical Medicine (FTM), Mahidol University (MU) and Dr. Sakura Sousa,
Director of International Anti-Aging and Regenerative Medicine Organization (IARO) was signed in 2023. The collaboration
between FTM, MU and IARO has been extensively expanded. Research on anti-aging product like Nicotinamidemononucleotide (NMN) has been started. The anti-aging marker detection such as telomere length measurement using Q
RT-PCR & Aging related cytokines (IL-1β, IL-6, IL-8, and TNF-α) detection using Bio-plex system, has been started.
The licensing plan for commercialization of therapeutic antibody against Dengue virus has been started. And the planfor production of INKT cell and other IPSC cell at FTM, MU has been started. So, since March 2024, the new IARO
Laboratory has been built at 12th floor, 50th year Anniversary building, FTM. MU. Two rooms of the total 50 Square Meters
was rented and renovated by IARO. One room is the main laboratory equipped with two Cell processing (CPC) machine,
Safety cabinet, freezer and liquid nitrogen tanks. The other room can be used as office and refrigerator to keep cleaned
products. Both rooms have equipped with Electronic cleaned air system.
The main mission of the new IARO Laboratory at Mahidol University is;
1.	Using CPC machine to Produce NKT cell for Senescent cell reduction and also to produce IPSc and Exosome forregenerative medicine.
2. Checking quality and tested the produced INKT, IPSC cells and Exosome.
3. Telomere length measured using Realtime Q PCR.
4. Detection of Aging related cytokines (IL-1β, IL-6, IL-8, and TNF-α) using Bio-plex system.
5. Rapid detection of multiple pathogens using Novel DNA Micro-Array system.
6. Research and development of therapeutic antibody against dengue virus and other diseases.
7.	Production of therapeutic and diagnostic monoclonal antibody (MAb) using novel single cell MAb production of the
Cytomine® System (UK).
With our great hope to help peoples to live better life using our cutting edge therapeutic and Anti-Aging products that being
proved by the world class research. The IARO Laboratory at Mahidol University will keep on trying our best to find new
innovation to help peoples.

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The Future of Medicine iPSC Technology Will Usher In
Koji Tanabe, Ph.D.
Founder&CEO- I Peace, Inc.

At I Peace, we are constantly considering how to swiftly bring about a world where iPSC technology genuinely improves andsaves lives. The Nobel Prize-winning iPSC technology has an extraordinary ability to reprogram aged cells into a youthfulstate, promoting longevity, personalized medicine, drug discovery, and autologous transplantation. Our vision extends to afuture where individuals routinely receive and preserve their iPSCs at birth, envisioning iPSC technology as a source of joy
and relief for millions enduring suboptimal quality of life, pain, and despair. We are committed to promptly realizing thisvision, striving to ensure universal access to iPSCs for clinical treatment and rejuvenation.
Our dedication to advancing iPSC technology stems from my tenure as a graduate student in Dr. Yamanaka’s lab at Kyoto
University. Over eight years, I had the privilege of collaborating with esteemed colleagues and contributing to several journal
publications and patents, including the seminal first human iPSC paper as a second author, which significantly influenced
my trajectory.
As the application of iPSC technology expands, so does recognition of its bottleneck—the exorbitant cost of producing
clinical-grade iPSCs ($1M per person), making it inaccessible to many. Additionally, there is a scarcity of organizations
capable of producing high-quality, clinical-grade iPSCs. I firmly believe that the transformative impact of any scientificfield is magnified when basic research findings are leveraged by industry. Merely automating conventional iPSC induction
processes falls short of our aspirations. Leveraging our expertise, we have pioneered a proprietary automation system capableof annually producing thousands of clinical-grade iPSCs, drastically reducing production costs and broadening accessibility.
Recently, we also succeeded in establishing a system for efficiently generating iPSC-derived somatic cells. These massproduced iPSC-derived cell products are valuable for personal care and drug screening. These innovations envision a future
where individuals routinely possess and utilize their own iPSCs from birth. It has been an exhilarating journey from a mere
vision and ambition in 2015 to our current standing. We will present the future of regenerative medicine and rejuvenation
therapy brought by iPSC technology.

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Immunotherapy for Cancer Using iNKT Cell and Next Generation
NKT Therapy With Drug Delivery System
Taehun Hong, Ph.D.
Research & Development Manager- Ambicion Co., Ltd.
Research Fellow- Department of Bioengineering, The University of Tokyo
Adjunct Assistant Professor- Department of Molecular Pathology, Tokyo Medical University
Co-authors:

Igarashi K, Li S, Matsuda K, Nakashima Y, Chen P, Cabral H
The University of Tokyo

Introduction Among the numerous challenges associated with aging, carcinogenesis stands out as one of the mostdevastating and fearsome issues. Despite the development of various antitumor drugs, many patients still lack a complete
cure, while others suffer from severe side effects. Immunotherapy using immune checkpoint inhibitors (ICIs) has emerged
as a promising approach for cancer treatment in recent years due to its low toxicity and ability to engage autoimmune cells
in self-cure. However, the instability of treatment effects in individual patients has hindered the achievement of satisfactory
outcomes in many cases. In this study, we propose a novel immunotherapy approach based on the activation of NKT
cells, independent of cancer type and patient characteristics. To implement this approach, we utilized a Drug Delivery
System (DDS) to create a nano-carrier that effectively delivers RK-163 to dendritic cells in the lymph nodes adjacent to thetumor. This delivery mechanism activates the NKT cells and enhances the immune system's ability to attack cancer cells.
Our method demonstrated successful suppression of 4T1 breast cancer growth, even in cases which showed resistance toconventional ICIs. Furthermore, it prolonged the survival of 4T1 tumor-bearing mice by five-fold. By implementing DDS
into the NKT activation method, we aimed to inhibit cancer growth in a cost-effective and simple manner for those cancers
that cannot be effectively treated with traditional immuno-cancer therapies.
Keywords immunotherapy for cancer; NKT cell activation; RK-163; Drug Delivery System; Immune checkpoint inhibitors.

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Problems of Speech and Swallowing in Human Beings, theAdditional Solutions with Regeneration, Instead of Just AntiAging
Koichi Tsunoda, M.D., Ph.D.
Department of Artificial Organs & Medical Creations/Otolaryngology National Hospital Organization Tokyo Medical Center

Last 40 Years, I developed many novel therapies for voice problems with satisfactory evidence to every citizen. With that, I
simultaneously took care with phono-surgery for voice problems of professional voice users including many top actors andsingers in Japan.
In contrast to other mammals, evolution has brought humans the long and flexible vocal tract needed for speech. The
human adult larynx is located in and has descended through the neck, resulting in an effective articulatory system that hasenabled the ability to communicate through speech. As a result, humans must elevate the larynx and move it anteriorly while
swallowing to prevent aspiration. The vocal folds themselves also participate in prevention of aspiration during swallowing
by closing the glottis. When aspiration does occur, action of the true and false vocal folds operates as part of the coughmechanism to expel foreign bodies (water, food). Laryngeal elevation and glottal closure are indispensable for human beings.
Anatomically and physiologically, atrophy of extrinsic and intrinsic laryngeal muscles due to aging gradually weakens thefunctions of laryngeal elevation and glottal closure, which causes hoarseness and aspiration. This results not only from glottal
incompetence, but also from lower position of the larynx and increased difficulty to elevate it. Surgical solutions require
strengthening the atrophic intrinsic and extrinsic laryngeal muscles. Many techniques involving injections inside intrinsic
laryngeal muscles, and laryngeal elevation surgery have been developed but have disappeared.
In 1998, I developed a surgical solution for insufficient glottal closure for phonation and aspiration called autologoustransplantation of fascia into the vocal folds (ATFV), that was within the new conception of regenerative medicine. We observed
histological changes and cell proliferation activity after ATFV, suggesting that fibroblasts transplanted into the fascia do notdegenerate but survive and proliferate in human Reinke‘s space. However, for Wermer’s syndrome, transplantation of fascia
leading to regeneration of vocal fold tissue, using a mechanism like stem-cell transplantation, was not effective. That might havebeen caused by the aged state of the stem-cells transplanted. Reproducible/promotable tissue transplantation is necessary.
Considering the swallowing function in the elderly, injection of reproducible/promotable stem-cells into atrophic vocal
folds may produce improvements for glottal incompetence and injections into laryngeal elevation muscles may produce
improvements for laryngeal elevation in swallowing. This technique, which prevents scar formation in the surrounding
tissues, would be preferable to invasive surgical incisions.
In combination with these simple injections of stem-cells into weakened muscles, drawing in the jaw during swallowing(easier laryngeal elevation by shortening the distance between the oral cavity and the larynx) and maintaining speech as selfrehabilitation (training to reinforce the glottal closure) may prevent future problems of aspiration in the elderly. Furthermore,
if velopharyngeal dysfunction (weakened changes of soft-palate elevation for phonation and swallowing) is recognized,
injection into the muscle of soft-palate elevation with suitable training (training to reinforce the soft-palate elevation) is
necessary.
Before those solutions, it is necessary to individually evaluate swallowing and phonatory functions as a medical check-up. To
rejuvenate aged senses and muscles with a view to improving an individual’s life as they age is important. For that, a novel
medical check-up program is needed to maintain and enhance quality of life, not only for speech and hearing, but also for
the function of the nose for smelling.
Keywords: Human; Phonation; swallowing; glottal closure, vocal fold, laryngeal elevation; intrinsic/extrinsic laryngeal
muscles; injections of reproducible/promotable tissue; prevention of aspiration
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Aging of the Olfactory System: Pathophysiology and Treatment
Strategies
Kenji Kondo, M.D., Ph.D.
Professor- Department of Otorhinolaryngology Head and Neck Surgery, The University of Tokyo

The sense of smell is involved in appreciating the smell of food, wine, flowers, or perfume, as well as in the physical safety
by detecting gas leaks and foul odors. The worldwide spread of COVID-19 has resulted in a large number of patients witholfactory dysfunction, which has made not only medical professionals but also the general public aware of the importance ofthe sense of smell. Compared to vision and hearing loss, olfactory dysfunction has been neglected in the past because it is lesssocially disabling, but patients with olfactory dysfunction have difficulties in many aspects of daily life.
The pathophysiology of olfactory loss can be divided into two main categories: conductive olfactory loss and sensorineuralolfactory loss. The former is typically caused by rhinosinusitis, which mechanically obstructs nasal airflow and prevents
odorants from reaching the olfactory mucosa. This pathophysiology can be treated by treating the underlying disease. On
the other hand, sensorineural loss is caused by dysfunction/degeneration of the olfactory neuroepithelium and the olfactory
neural pathway. Sensorineural olfactory loss is difficult to treat and there is currently no evidence-based medication.
Age-related olfactory dysfunction is one of the major categories of sensorineural olfactory dysfunction. Our recent researchaims to elucidate the pathophysiology of age-related olfactory dysfunction and to develop effective methods to prevent/treat it. Previous animal studies have shown that aging is associated with a decrease in the number of olfactory neurons in
the olfactory mucosa, as well as the degeneration of supporting tissues such as olfactory glands and supporting cells. The
decrease in the number of olfactory neurons appears to be due to a decrease in the proliferation of basal cells, which are stem
cells, in both normal and injured mucosal conditions. The accumulation of lipid peroxide in the olfactory mucosa with aging
suggests that oxidative stress is one of the factors contributing to age-related degeneration of the olfactory mucosa. Thesestudies suggest that treatment to reduce oxidative stress in the nasal cavity may be useful in preventing age-related olfactoryloss, and drugs that stimulate basal cell proliferation may be candidates for the treatment.
In addition to these findings in sensorineural tissues, we also found that the metabolic capacity of olfactory mucus and
LCN15, a specific protein of olfactory mucus, decreases with age. These molecular mechanisms potentially involved in
olfactory perception may also be a future therapeutic target for sensorineural olfactory dysfunction.

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Ultra-Low Dose Computed Tomography Combined with
Artificial Intelligence for Enhanced Health Screening: A Nexusof Evidence, Innovation and Integrative Medicine
Richard H. Kaszynski, M.D., Ph.D.
Executive Director- Advanced Medicine Center, SENSHIN CLINIC
Director, Stanford Solutions, Stanford University School of Medicine

The integration of artificial intelligence (AI) with medical imaging technologies is revolutionizing diagnostic accuracy andpatient safety in health screening. In the present lecture, we introduce a pioneering system that combines Ultra-Low Dose
Computed Tomography (ULD-CT) with advanced diagnostic AI, presenting the world's first screening system specificallydesigned for comprehensive health screening. This innovative system capitalizes on the reduced radiation exposure of ULDCT while leveraging AI's capability to enhance image analysis, thereby mitigating the traditional limitations associated withlower-dose CT scans. The present ULD-CT + AI system employs a series of state-of-the-art AI algorithms enabling theidentification and evaluation of clinical radiographic features with high precision. The AI component not only compensates
for the potential decrease in image quality due to reduced radiation but also enhances detection rates of subtle pathologicalchanges, which are often missed in standard imaging protocols.
The AI algorithm supports real-time analysis, providing immediate feedback that is essential for early disease detection andmanagement. The implementation of this system in a clinical setting has demonstrated a significant reduction in radiation
exposure—up to 93% compared to conventional CT scans—without compromising diagnostic accuracy. This reduction isvital for population-based screenings, particularly in high-risk groups where repeated imaging may be necessary. Preliminary
studies using the present combination of ULD-CT + AI have shown promising results in detecting early-stage diseases,
including cancers and vascular disorders, which are often asymptomatic in their initial stages. By enabling earlier detection
and intervention, our system has the potential to improve patient outcomes significantly and reduce healthcare costs
associated with late-stage treatments. The ULD-CT + AI system represents a significant advancement in medical imaging
technology. It exemplifies how AI can transform health screening, making it safer, faster, economical and more accurate.
Future studies and broader implementations are planned to further validate the effectiveness and adaptability of this system
across various clinical scenarios.

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Sponsors
クオール株式会社 / Qol Co., Ltd.
株式会社バイオジェノミクス / Biogenomics Co., Ltd.
株式会社SOPHIA / SOPHIA Co., Ltd.
亜細亜食品株式会社 / Asia Shokuhin Co., Ltd.
株式会社グラツィア / Grazia Co., Ltd.
株式会社シャリオン / CHARION Co., Ltd.
株式会社ONEST / ONEST, Inc.
SENSHIN CLINIC

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