Moonshot Research and Development Program

MOONSHOTGOAL-7

To Age 100 without Health Concerns

MOONSHOT

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
Creating a society in which everyone can stay healthy into old age will not just reduce the burden on medical andsocial care in a super-aging society, but more importantly will enable us to live fuller and more active lives.
In addition to disease prevention, effective treatment methods mean that many illnesses are expected to become
treatable ailments. In this environment, if only we could enjoy life free from the effects of aging!
This is humanity’s universal dream, and the creativity that can imagine achieving this goal and the technologies
and newly understood mechanisms that will be developed thanks to this motivating force will provide new
impetus to bring us a wonderful future.

Three targets for meeting this goal
TARGETTARGETTARGET

Realization of a society where
everyone can prevent diseases
spontaneously in daily life

Realization of medical networks
accessible for anyone fromanywhere in the world

Realization of drastic
improvement of QoL without
feeling load

Establish infrastructure to maintain goodmental and physical health by developing
technologies using regulation of immune
systems or sleep, etc. in order to stayhealthy and prevent the onset andexacerbation of diseases, and technologies
to visualize individual physical and mental
state in daily life and urge people tovoluntarily take health maintenance actions
most suitable for them.

Establish a medical network functioning
regardless of region and even during disasters
and emergencies to provide the same level of
medical care as normal times by developing
diagnostic and treatment devices for simple
tests and treatments at home, etc. anddiagnosis- and treatment-free technologies forsome chronic diseases.

1

Moonshot Goal-7 Program2

3(realization of an inclusive society
without health disparity)
Establish a social infrastructure to enableself-reliant life at home without depending on
nursing care by developing such technologies
as the recovery of body function withrehabilitation without feeling burdened,normalization of ailing biocontrol systems,
regeneration or substitution of weakened
organs and so forth.

This program aims to achieve the goal established by Japan's Headquarters for Healthcare Policy.
More details are available from the Cabinet Office, Government of Japan website. https://www8.cao.go.jp/cstp/english/moonshot/sub7_en.html

Improving mitochondrial function to extend life expectancy

Keeping healthy to the best life
Development of method for complex tissue regeneration
via tissue embryonization

Regenerating lost limbs
Ended November 2023

Extending healthy lifespan by eliminating senescent cells

Eliminating the cause of aging

Regulating microinflammation: Preventing disease
through quantum and neuromodulation technologies

Picking up disease warnings quickly

PROJECTS

Deciphering and Engineering Sleep and Hibernation -The Future of Medical Care

Bringing healthy sleep to people
throughout the world
Bring hospital into home toward controllinginflammation at home

Burden-free health management
Understanding and harnessing the role of the gut microbiomein healthy longevity

Harnessing the power of the
microbiome for health
A world of zero cancer risk created by rejuvenation
using cell lineage conversion

Making cancer a thing of the past

Actualization of a cancer-free society

Bringing the cancer rate down to zero

GOAL-7 KEYWORD
Extending Healthy Longevity“Healthy longevity” refers to being able to live in the self-awareness of health, without restrictions
on activities or chronic disease. The Moonshot Goal 7 aims to make the difference between
average life expectancy and healthy life expectancy, that is, the time for which someone is ill or
requires social care (the unhealthy period), as close to zero as possible, with the goal of achievinga society in which everyone can stay healthy into old age.

Average life expectancy and healthy life
expectancy of Japanese people

Average life expectancy
Healthy life expectancy

Unhealthy period
2019

Men: 8.73 years
Women: 12.07 years

Age 81.41

Men

Age 72.68

8.73 years

Age 87.45

Women

Age 75.38
60

65

70

75

Get the unhealthy
period as close tozero as possible

12.07 years
80

85

90 (Age in years)

Source: Compiled by AMED using data from Ministry of Health, Labour and Welfare “Abridged Life Tables for Japan 2020” for average life expectancy and data from “Research Concerning
Calculation and Assessment of Healthy Life Expectancy and Prediction of Extension of Healthy Life Expectancy” a research report of the committee for “Comprehensive Assessment of Health
21 (the Second Term) and Research for the Next National Health Promotion Movement Plan”, funded by Foundation for Health, Labour and Welfare Policy Research Grants from the Ministry of
Health, Labour and Welfare of Japan 2021 (Comprehensive Research Project on Cardiovascular Diseases, Diabetes and other Lifestyle-related Diseases) for health life expectancy.

MOONSHOT
GOAL-7

The aim is to build healthand social care systems by 2040
that mean people can enjoy
living until they turn 100.
Program Director HIRANO Toshio

Our theme is overcoming chronic inflammation,
which underlies a whole raft of diseases.
When we catch a cold or injure ourselves, an inflammatory

and patients can be expected to make an effort to follow thisreaction occurs inside our bodies. This inflammation (acuteadvice. In Moonshot Goal 7, we are engaged in research andinflammation) is well controlled, and subsides over time.

development that adopts a range of approaches to this

Chronic inflammation, on the other hand, occurs when thisprocess of advice leading to prevention and treatment fromcontrol stops working and the inflammation persists long-term.

the viewpoint of biomedical sciences, including inflammatory

While aging promotes chronic inflammation, the reverse issubstances within the body, mitochondrial function, andalso true. Chronic inflammation associated with aging is one ofsenescent cells, with the goal of providing lifestyle advice

the main causes of a raft of age-related diseases, including

through medical networks as well as preventive treatment

cancer, arteriosclerosis, diabetes, and dementia. If suchwhen required, in order to bring the “unhealthy period” during

chronic inflammation could be controlled, this might help

which people are bedridden or otherwise incapacitated to as

prevent age-related diseases and reduce the gap between

close to zero as possible. If this goal can be achieved, it would

average life expectancy and healthy life expectancy. Even

give people the chance to enjoy a new lease of life, which

under normal circumstances, if BMI calculations show thattoday might not be considered possible because of age-related

visceral fat has increased, this can cause chronic

health concerns. They will be able to pursue their dreams

inflammation. It is thought that if such chronic inflammation

once again in their 60s. That means they get to live life twice

continues to increase, it may become a cause of cancer andover. I am committed to this goal of extending healthy

many other age-related diseases. Doctors will advise people tolongevity by even a single day because I want everyone’s lives

reduce their visceral fat by improving their diet and exercising,

to be bright, enjoyable, and positive right up to the end.

Toward achieving sustainable health and social care systems

Three Targets

1

Everyone can prevent diseases
spontaneously in daily life

The goal is to create medical networks to prevent disease

Smartwatches enabling people to monitor their heart ratemeasures such as exercise and diet or sending a message

and the number of steps they take are already widely

saying “If you go on like this you’ll be in trouble” to theavailable, but to discover the levels of inflammatory

individual’s smartphone or other device. This means that

substances, sugar, cholesterol, and other substances in theirindividuals will be able to receive their normal preventive

blood, people still need to have blood drawn in a medical

measures or treatment via these networks wherever they are

institution. If devices can be developed for the simple

in the world, or during extraordinary circumstances such asmeasurement of these data (biological trends) and to collectnatural disasters. Making this a reality would greatly reduce

urinary and fecal data from toilets, this will enable daily data

both the staff and costs required for medical and social care.

to be checked on an everyday basis, which would encourage

and aging levels could also be evaluated at the same time.

3

Based on such data, it should be possible to extend healthy

When people’s health deteriorates, whether by hearing loss

longevity not just by improving people’s lifestyles from theor due to illness such as heart disease, this generates

medical perspective, such as through diet, exercise, anda difference between them and healthy people (healthsleep, but also by eliminating senescent cells and nipping

disparity). The aim is to reduce this difference to as close tochronic inflammation in the bud.

zero as possible. As well as preventing disease, this means

2

maintaining Quality of Life (QoL) from treatment to

individuals to do something about it, meaning that disease
could be prevented before it starts. Presymptomatic disease

Medical networks accessible
for anyone from anywherein the world

before it can occur by conducting medical interventions at the
pre-disease stage, such as recommending preventive

Drastic improvement of
QoL without feeling load

rehabilitation by providing care and treatment that place as
little strain as possible on the body in order to shorten the
difference between actual life expectancy and healthy life

Senescent cells are increasing without our knowledge, even

expectancy. The goal is to maintain QoL until the end of eachin healthy people who are leading normal lives in society.

individual’s life.

HIRANO Toshio Program Director
Professor Emeritus, Osaka University, and Director, Osaka Heavy Ion Therapy Center
After graduating from Osaka University Faculty of Medicine in 1972, Hirano studied at the US National Institutes of Health andworked at Osaka Habikino Medical Center before becoming an assistant professor at Kumamoto University. He then moved backto Osaka University as an assistant professor and was then appointed full professor, after which he became Dean of the Graduate
School of Frontier Bioscience, Dean of the Graduate School of Medicine and Faculty of Medicine, and eventually the 17th
President of Osaka University. He has been a member of the Science Council of Japan, President of the Japan Society of
Immunology, a member of the Council for Science, Technology, and Innovation, and President of the National Institutes for
Quantum and Radiological Science and Technology, among other positions. His awards include the Sandoz Prize for Immunology,
the Fujiwara Prize, the Crafoord Prize, the Japan International Prize, and a Clarivate Citation Laureate 2021 in Physiology or
Medicine, and he has received the Medal with Purple Ribbon and the Grand Cordon of the Order of the Second Treasure. He

HIRANO Toshio

discovered interleukin-6 (IL-6), and identified its mechanism of action and its association with chronic inflammatory disease.

Improving mitochondrial function to extend life expectancy

Keeping healthy to the best life
Inside the body...

Today’sreality

The function of the mitochondria,
which produce the fuel forthe energy expended in activity,
has declined

As we age, our physicaland mental functions
decline (frailty)

Sugar
and oxygenFree
oxygenradicals● Condition intermediate between good

health and requiring social care

● Declining physical and mental

ATPfunction● Treatment and prevention alone are
not enough(energy)

D R E A M IN G P O W E R

Active, invigorated mitochondria

Our
dream

Mitochondria are restored tohealth, producing the fuel forthe energy expended in activity

Released from the “aging
phenomenon” that weakens
the body, while potentiallyalso protected against
cancer and dementia

Sugar
and oxygenFree
oxygenradicalsATP(energy)

Mitochondrial preemptive medicine
Mitochondria are the organ that produces most of the energy expended in activity. Identifying the relationship between
aging and these mitochondria, which are essential to keeping healthy, will be useful for diagnosing mitochondrial
function in a way that does not place strain on the body, and for the development of treatment drugs. Our goal is asociety in which people can achieve a healthy old age until they turn 100, by enabling the prevention and treatment of
a whole raft of diseases including chronic inflammation, which occurs when mitochondrial function declines.
Therapeutic agent MA-5, now inclinical trials

Improving mitochondrial function to extend life expectancy

Keeping healthy to the best life

FOR THE FUTURE
Our goal is to detect mitochondrial functional decline as early as possible and provide
intervention or treatment in order to build a society in which people stay healthy into old age.
When mitochondrial function goes wrong, it has been shown to bea cause of diseases including deafness, sarcopenia, ALS, andParkinson’s disease. However, a simple method of assessing
mitochondrial function has yet to be established. Not only such anassessment method but also ways of improving mitochondrial● Establish methods of diagnosing and treating the various diseases

caused by a decline in mitochondrial function● Enable the simple detection at home of age-related mitochondrial

functional decline from breath, urine, saliva, or similar samples, andfunction with drugs, diet, or exercise are keenly awaited. One

help improve their weakened mental and physical state by indicating

pioneering drug is MA-5, which is currently in clinical trials forthe optimum diet and exercise for that person

diseases caused by midochondrial dysfunction.

● Establish drugs to treat the diseases caused by adecline in mitochondrial function● Develop sensors to measure mitochondrial function● Link the data from the sensors to a database, andestablish systems to suggest measures such as

rehabilitation, oral care, diet, and medications thatare appropriate to the individual concerned to
improve their weakened mental and physical state

TODAY

2030
TARGET

2040
BREAKTHROUGH

ABE Takaaki Project Manager
Professor, Tohoku University Graduate School of Biomedical Engineering

After graduating from Tohoku University, Abe continued to study at Tohoku University Hospitaland Kyoto University Graduate School of Medicine, gaining a doctorate in medicine. He went on
to a postdoctoral fellowship (PD) at the Japan Society for the Promotion of Science, before
moving to Harvard Medical School as a postdoctoral fellow in the Human Frontier Research
Program. On his return to Japan he conducted research into kidney disease and hypertension
as a JST PRESTO project while working in the Division of Nephrology, Endocrinology, andHypertension of Tohoku University Medical School. Since 2008 he has been a professor in the
Tohoku University Graduate School of Bioengineering and Tohoku University Graduate Schoolof Medicine. He was appointed an AMED Moonshot Project Manager in 2020.

ABE Takaaki

Extending healthy lifespan by eliminating senescent cells

Eliminating the cause of aging

Today’sreality

er

nc

Ca

es

Diabet● The body ages as we grow older,both in ways we can see and inways we can’t● Aging and its associated diseases
must be treated individually

Ki

Arteriosclero

dn

ey

fa

sis

ilu

re

D R E A M IN G P O W E R

Develop the technology to eliminate senescent cells

Our
dream

● Prevent age-related changes inthe body● Overcome every type of disease

for which age is a cause

Senescent cells
Chronic inflammation due to the accumulation of “inflammation-inducing cells”, such as senescentcells, causes aging and diseases of old age. Our goal is to prevent and treat the entire range of
diseases for which age is a cause by eliminating senescent cells, which increase with age, from thebody and suppressing inflammation.
Callianthemum hondoense, found near mountain peaks in
the Southern Alps of Japan. They date back to the glacial
period, and have fresh, vibrant flowers.

Extending healthy lifespan by eliminating senescent cells

Eliminating the cause of aging

FOR THE FUTURE
Improve aging and eradicate the entire range of age-related diseases
by removing the senescent cells that cause chronic inflammation.
Currently, age-related decline in physical function and a diverse range of● Develop the technology to remove senescent cells, so

diseases are all dealt with by treating them individually. However, if thegetting rid of age-associated disease and organ failure

senescent cells that cause chronic inflammation could be eliminated, this might● Establish techniques for measuring the level of aging

enable the entire range of age-related diseases to be overcome. We are engaged

and its speed, and construct systems for measuring
the effects of removing senescent cells

in research to prevent senescent cells from accumulating within the bodydespite advancing age. Our ultimate goal is to achieve the ultimate in preventive
medicine by enabling the degree of progression of aging to be easily measurable
at home and for this information to be shared with family doctors, so thatsenescence can be dealt with before disease symptoms appear.

● Implement the world’s first clinical trialsof chemical substances that remove
senescent cells● Build the technology to measure the levelof aging and its speed

TODAY

2030
TARGET

2040
BREAKTHROUGH

NAKANISHI Makoto Project Manager
Professor, Division of Cancer Cell Biology, The Institute of Medical Science,
The University of Tokyo

After graduating from university, Nakanishi spent a year in clinical research before embarking
on a career in basic research to pursue his interest in the aging of individuals. In 1993 he went
to study in the United States, where he began studying cellular senescence in detail. From2000 he joined the Nagoya City University Graduate School of Medical Sciences, where hestarted studying the induction mechanism of cellular aging by DNA damage. He then moved to
the Institute of Medical Science of The University of Tokyo in 2016, where he put together alaboratory to engage in research with the goal of identifying the regulatory mechanism ofindividual aging. Since 2023 he has been the Director of The Institute of Medical Science, withNAKANISHI Makoto

responsibility for leading the entire institution.

Regulating microinflammation:
Preventing disease through quantum and neuromodulation technologies

Picking up disease warnings quickly

Today’sreality

Inflammat!?

ion● Disease-causing

microinflammation isundetectable● Microinflammation is
impossible to eliminate

D R E A M IN G P O W E R

Unleash the power of quantum
and neuromodulation technologies

Our
dream

I n fla mm ation● Detect microinflammation at avery early stage by quantum tech

● Prevent disease by eliminating

microinflammation byneuromodulation techMembers of Professor Murakami’s lab, award celebrations

Immune cells
and IL-6 amplification

Gateway reflex
and inflammatory reflex

Inflammation causes a wide range of diseases,
but this requires the activation of both immune
cells in the blood and non-immune cells intissues. Factors and other substances from
activated immune cells act to activate IL-6
amplification in non-immune cells in tissues,and the overproduction of IL-6 and migration
factors may induce inflammation, resulting indisease.

Stress, pain, and other environmental stimuli each activate
different neural circuits. These activated neural circuits
create gateways for immune cells in the blood to invade
tissues, activating IL-6 amplification at specific vascularsites and causing disease. This mechanism of diseaseinduction by neural circuits is called the “gateway reflex”.
The phenomenon whereby activated vagus neural circuits
suppress the immune system is known as the “inflammatoryreflex”.

Regulating microinflammation: Preventing disease through quantum and neuromodulation technologies

Picking up disease warnings quickly

FOR THE FUTURE
Use the power of quantum and neuromodulation technologies
to achieve the ultra-early discovery and elimination of disease.
We are engaged in research to identify signs of disease from the expression levelsof specific genes in immune cells in the blood and non-immune cells in tissues, andto investigate the activation of IL-6 amplification to assess organs that are
inflamed, with the aim of understanding “microinflammation” before it reaches thestage of chronic inflammation. For example, we are attaching stick-on electrodes tothe body to control the activation of neural circuits where the gateway reflex or the
inflammatory reflex occurs, with the aim of blocking the invasion of tissues andorgans by inflammatory cells that attack their own body and nipping● Develop technology for the detection and elimination of

microinflammation based on research on the
inflammatory reaction and various forms of big data
analysis● Connect small wearable devices to AI-controlled big
data analysis systems, and develop a system foreliminating systemic microinflammation wherever a
person may be.

disease-causing microinflammation in the bud, which may help prevent
autoimmune diseases and perhaps even dementia and arteriosclerosis.

● Establish a method for the ultra-early/ultra-sensitive

detection of microinflammation by using genetic analysis ormolecular sensors to investigate blood, urine, and tissues● Validate the effectiveness of technologies to pick up signsof disease by artificially stimulating specific neural circuits● Develop AI technology to predict the onset of
microinflammation on the basis of big data gathered bymeans such as sensors

TODAY

2030
TARGET

2040
BREAKTHROUGH

MURAKAMI Masaaki Project Manager
Professor, Hokkaido University Institute for Genetic Medicine

After graduating from the Faculty of Veterinary Medicine of Hokkaido University, Murakami
obtained a PhD from Osaka University on the IL-6 signal transduction mechanism. He
subsequently studied T-cell immunology at Hokkaido University and in the U.S. and conducted
research at Osaka University on the relationship between IL-6 and disease, in which hediscovered IL-6 amplification and the gateway reflex. He is currently affiliated with the
Hokkaido University Institute for Genetic Medicine, while also pursuing the elucidation of themechanism of onset of rheumatoid arthritis and other inflammatory diseases in laboratories at
the National Institutes for Quantum Science and Technology and the National Institute forPhysiological Sciences.

MURAKAMI Masaaki

Deciphering and Engineering Sleep and Hibernation -- The Future of Medical Care

Bringing healthy sleep to people
throughout the world

Today’sreality● Accumulated sleep

debt causes a range ofdifferent disorders● One in four people is troubled
by insomnia or feeling sleepy
during the day

D R E A M IN G P O W E R

Unlock the mystery of sleep to control sleeping

Our
dream

● Prevent disease throughhigh-quality sleep● A world in which everyone ishappy with how they sleep

Sleep debt
Although the amount of sleep needed for physical and mental health varies between individuals, on
average Japanese people sleep much less than people in other nations, and the great majority ofstudents and those of working age are not getting sufficient sleep in Japan. The accumulated sleep
deficits lead to “sleep debt”, and as this can be a cause of depression, metabolic syndrome, anddementia, hopes are growing for the development of technology capable of controlling sleep at need.
Device for measuring brainwaves during sleep

Deciphering and Engineering Sleep and Hibernation -- The Future of Medical Care

Bringing healthy sleep to people throughout the world

FOR THE FUTURE
Unlock the secrets of “sleep” and “hibernation”
for a life untroubled by sleep-related issues
Sleep insufficiency and chronic inflammation are known to have a causal relationship● Prevent the onset and exacerbation ofwith each other, and as well as identifying its specific mechanisms, predicting thediseases caused by sleep problems by
developing the technology to regulate
non-REM and REM sleep, and sleep deficit bydevising sleep-debt risk prediction systems● Revolutionize emergency medicine throughartificial hibernation technology, dramaticallyreducing mortality and morbidity

health risk due to sleep deficits, such as the development of chronic inflammation in
the form of metabolic syndrome, and elucidating how this works will be the key.
To achieve this, the goal is to build sleep big data to understand the whole picture ofJapanese people’s sleep and to clarify the control mechanisms and functions of sleep.
Through this, our aim is to resolve a range of sleep-related issues and realize a society
where everyone can prevent diseases through sound sleep in daily life. Making
artificial hibernation practicable could also save lives otherwise lost during emergency
situations, which would revolutionize emergency medicine.
● Discover clues to drugs that can adjust the optimum

sleeping time

● Discover clues to drugs that can adjust the REM

sleep needed to refresh the brain● Use big data analysis to develop a system forpredicting sleep-debt risk

● Discover clues to drugs and technologies that enableartificial hibernation

TODAY

2030
TARGET

2040
BREAKTHROUGHYANAGISAWA Masashi Project Manager
Director/Professor, International Institute for Integrative Sleep Medicine,
University of Tsukuba

Yanagisawa obtained MD and PhD degrees at the University of Tsukuba. He is the discoverof the endothelial vasoconstrictor endothelin and of orexin, a neurotransmitter that
regulates the sleep/wake cycle. In 1991, aged 31, he moved to the United States, as aprofessor at the University of Texas Southwestern Medical Center and an investigator of the
Howard Hughes Medical Institute. In 2010 he also established a research laboratory in the
University of Tsukuba. Since 2012 he has been Director and Professor of the World PremierInternational Research Center Initiative-International Institute for Integrative Sleep Medicine(WPI-IIIS). He is also the CEO of S’UIMIN and a member of the U.S. National Academy of

YANAGISAWA Masashi

Sciences. He was awarded the 2023 Breakthrough Prize in LIfe Sciences.

Bring hospital into home toward controlling inflammation at home

Burden-free health management

Today’sreality
Diabetes, cancer, and otherlifestyle-related diseases aremanaged in hospital● People attend hospitals for detailed

tests and large-scale treatment● There are limits on the number ofhospital visits, and getting to thehospital is a strain in itself● Patients who live a long way from
hospital may not be seen until
too late

D R E A M IN G P O W E R

Develop “medical networks”

Our
dream

● Easily collect physical data athome, and discover and treat
lifestyle-related diseases at the
pre-disease stage● Eliminate healthcare disparities
between regions, and establish
healthcare services that are
equally accessible from anywherein the country

HOSPITAL

Medical networks
Use data on “skin gases” (the vapor emitted from the surface of the skin) collected at home using
smart digital devices for analysis and diagnosis in hospital. Networks connecting homes andmedical institutions will enable people who find it difficult to get to hospital to undergo tests andreceive medical care. This mechanism will revolutionize remote medicine and help build a society inwhich lifestyle-related diseases are no longer a concern.
Ultra-low-concentration gas analyzer measuring simulatedskin gasBring hospital into home toward controlling inflammation at home

Burden-free health management

FOR THE FUTURE
Connect hospitals and homes via digital devices, to build a society
in which everyone can overcome lifestyle-related diseases
The development of smart digital devices to measure “skin gases”, which are an
indicator of health, will enable the at-home diagnosis of the chronic inflammationthat causes lifestyle-related diseases, and the very early discovery of disease. As
well as building medical networks to connect hospitals and homes via digital
devices, research and development is also underway on treatment methods suchas electromagnetic stimulation and drugs that have effects similar to those of
exercise. Making remote medicine a reality and enabling inflammation to be● The collection of skin gas data means that the stateof inflammation can be checked without obvious
intervention, imposing no burden on the body
● Working toward a society in which therapies anddrugs with similar effects to those of exercise are
revolutionizing remote medicine

controlled at home will help to overcome lifestyle-related diseases, something thatis highly significant for Japan’s ultra-aging society.

● Build systems to collect and analyze skin gases, anduse this information in conjunction with data on
exercise, sleep, and diet
● Develop smart digital devices capable of measuring
the state chronic inflammation in daily life
● Develop therapies as alternatives to exercise, andimplement the appropriate treatment for individuals
at home

TODAY

2030
TARGET

2040
BREAKTHROUGH

NANGAKU Masaomi Project Manager
Professor, The University of Tokyo Hospital

Having graduated from The University of Tokyo School of Medicine in 1988, in 1994 Nangaku
went on to work in the Department of Nephrology of the University of Washington before
becoming a professor in the Division of Nephrology and Endocrinology of the Graduate Schoolof Medicine of The University of Tokyo in 2012. In 2023 he was appointed Dean of the
Graduate School of Medicine and Faculty of Medicine of The University of Tokyo. He is thecurrent President of the International Society of Nephrology, President of the Japanese Societyof Internal Medicine, and President of the Japanese Society of Nephrology. He is currently
engaged on elucidating the pathophysiology of kidney disease on the basis of oxygen biology
and developing treatment methods, as well as working for the innovative development of

NANGAKU Masaomi

remote medicine by providing a range of advice to the Japanese Medical Science Federationon the right way to extend these services.

Understanding and harnessing the role of the gut microbiome in healthy longevity

Utilizing the power of the microbiome
for healthToday’sreality？

● Much remains unknown

about how the gut
microbiome affects health● Chronic inflammation,
Alzheimer’s disease,and Parkinson’s
disease are difficult
to cureGut
microbiome

D R E A M IN G P O W E R

Understand the mechanisms
and actions of gut microbiome metabolites

Our
dream

!!

Gut
microbiome● Use gut microbiome metabolites tocontrol the immune system andchronic inflammation● Achieve the prevention and treatmentof chronic inflammation, Alzheimer’s
disease, and Parkinson’s disease

The gut microbiome
Our intestines are host to around 1000 species of gut bacteria, and their roles include maintaining
the body in a certain state. There are known to be between 100,000 and 200,000 gut microbiome
metabolites, and if simple tests to measure these could be developed by identifying the changes
they cause in the body and their chemical structures, these would immediately provide large
quantities of data that would be useful for the early discovery and prevention of disease.
Full staff meeting in May 2023

Understanding and harnessing the role of the gut microbiome in healthy longevity

Utilizing the power of the microbiome for health

FOR THE FUTURE
Discover gut bacteria involved in the control of chronic inflammation, and make use ofthem for prevention and treatment to achieve a society with healthy longevity.
Gut microbiome metabolites can act directly on the networks that link the intestinal tract
and the brain. Artificially regulating these actions may help control chronic inflammationand lead to treatments for neurological diseases such as Alzheimer’s disease andParkinson’s disease. Gut microbiome metabolites also function to activate and inhibit theimmune system, and we are researching immune system interventions using bothbacteria themselves and their metabolites. Our goal is to be able, for example, to put
together a “microbial cocktail” and supplement metabolites that are lacking in order to● Enable health management through theanalysis of gut microbiome metabolites● Intervene in the gut microbiome by direct

action or dietary improvements● Prevent and treat chronic inflammationand neurological diseases with microbial
cocktails

treat particular diseases.
● Unravel the actions and mechanisms ofthe tens of thousands of gut microbiome
metabolites● Identify gut bacteria and gut microbiome
metabolites that extend healthy longevity● Understand and utilize the mechanismthat connects the gut and the brain● Discover gut bacteria that control chronic
inflammation, and develop methods ofintervening in the neurological andimmune systems.

TODAY

2030
TARGET

2040
BREAKTHROUGH

HONDA Kenya Project Manager
Professor, School of Medicine, Keio University
After graduating from Kobe University School of Medicine in 1994, Honda took up a post in the
Department of Radiology of Kobe University School of Medicine until 1997. From then until 2001 heworked as a doctor in the Department of Gastroenterology of Kyoto University School of Medicine while
researching the origin of gastrointestinal immune tissue as a graduate student in the Department of
Molecular Genetics in the Graduate School of Medicine of that university. Between 2001 and 2007 he
was an adjunct in the Department of Immunology of Tokyo University Graduate School of Medicine, andfrom 2007 to 2009 he was Assistant Professor in the Department of Immune Regulation of Osaka
University Graduate School of Medicine. Between 2009 and 2013 he was Associate Professor in the
Department of Immunology of Tokyo University Graduate School of Medicine. In 2013 he became Team

HONDA Kenya

Leader of the RIKEN IMS Laboratory for Gut Homeostasis, a position he still holds, and since 2014 hehas been Professor in the Department of Microbiology and Immunology of Keio University School of
Medicine. He has been conducting research on the gut microbiome since 2007.

A world of zero cancer risk created by rejuvenation using cell lineage conversion

Making cancer a thing of the past

Today’sreality

Cancerous
cells● Cells keep on getting older● Cancerous cells continue toproliferate with the help of
their surrounding cells

D R E A M IN G P O W E R

Use the positive aspect of chronic inflammation
to try and return tissue to its original state

Our
dream

● Senescent cells are

rejuvenated● The cells surrounding

cancerous cells recover
their ability to inhibit
cancer growth

Cell lineage conversion
Cells continually change their state in response to environmental stimuli and changes within the
body. The alteration of the functions and roles already possessed by cells and the acquisition of new
properties and characteristics is called “cell lineage conversion”, and we are engaged in research to
do this artificially so that cells will be helpful in suppressing cellular aging. The well known iPS cellresearch also utilized cell lineage conversion.
RIKEN Yokohama Campus

A world of zero cancer risk created by rejuvenation using cell lineage conversion

Making cancer a thing of the past

FOR THE FUTURE
Bring the risk of cancer down to zero, to create a society
in which cancer is no longer something to be feared
Chronic inflammation was formerly thought of as a state in which the body’s● Develop technologies that intervene in cancer cells

action to return changes to their original state (homeostasis) had broken down,

and their surrounding networks via cell lineage
conversion● Act preventively on precancerous cells to reduce therisk of cancer to zero
● Global extension of medical and preventive
technologies

but it is now known that it also acts to push back the state of weakened
homeostasis to the surrounding area, evening out the level of cell aging andrejuvenating (reprogramming) cells. If this reprogramming mechanism could be
used to induce cell lineage conversion, this might enable tissues to be controlled,
and we are conducting research on treatment methods to suppress the growth ofcancer by returning cancer cells and the cells surrounding them that assist incancer growth to their normal state.

● Unravel the mechanism by which

senescent cells and chronic
inflammation induce cell lineage
conversion● Understand how cell lineage
conversion changes cancer cells andtheir surrounding networks

TODAY

2030
TARGET

2040
BREAKTHROUGHKOSEKI Haruhiko Project Manager
Deputy Director, RIKEN Center for Integrative Medical Sciences

After obtaining a Ph.D. at Chiba University Graduate School of Medicine in 1990, Koseki spenttime as a postdoctoral researcher at the Max Planck Institute of Immunology and was
Associate Professor in the Chiba University School of Medicine before being appointed
Professor in the Graduate School of Medicine in 1998. He has been working at RIKEN since2004. His research focuses on developmental genetics, in particular understanding epigenetic
regulation in morphogenesis and cell differentiation in mammals. He is also involved in joint
research on human diseases bringing together researchers from different fields, and isrunning investigator-initiated clinical trials in partnership with Chiba University and othercenters toward the development of new cancer immunotherapies using NKT cells derived

KOSEKI Haruhikofrom iPS cells.

Actualization of a cancer-free society

Bringing the cancer rate down to zero
Inside the body...

Today’sreality

Immune cells eradicate abnormal
cells from the body
Cancercells

Cancer treatment starts
after its diagnosis● The mechanism that determines whether

abnormal cells that have developed within
the body will become a cancer or be
elminated from the body by the immune
system is still poorly understood● Cancer is the top cause of death among
Japanese people, and its rate is increasing
every year

Immunecells

D R E A M IN G P O W E R

Ability to accurately predict
the behavior of abnormal cells within the body

Our
dream
Understand the risk ofcancer before it develops,
and be able to treat it withlifestyle improvements andsimple treatment

Discover cancer and its origins at a very early stage
The abnormal cells that are the origin of cancer are generated in the body by chronic inflammation, and we are working
to identify the mechanism that determines whether or not they turn into clinical cancer, thereby this can be predictedaccurately. The establishment of technologies to monitor abnormal cells in the body through the highly sensitive
detection of immune responses and genetic alterations in these abnormal cells can accurately predict the risk to
become clinical cancer. This means that cancer and precancerous abnormal cells will be detected at a very early stage.
Considering the diversity of the immune responses, we collect the overseas data to identify a universtal biomarker(s) that
Equipment for visualizing interactions between immune
cells and other immune cells or target cells

can precisely predict cancer risk and are applicable for a wide range of peple.

Actualization of a cancer-free society

Bringing the cancer rate down to zero

FOR THE FUTURE
Detect precancerous chronic inflammation andachieve a cancer-free society through very early treatment
Treatment for advanced cancer often takes a long time and imposes a heavy physical● Predict the cancer risk from theand mental stress. If the abnormal cells generated by chronic inflammation and theimmune responses to these cells could be detected with high sensitivity, and then, thedevelopment of abnormal cells generated
by chronic inflammation, and provide
appropriate preventive treatment● Build a system to detect the minutechanges in cells caused by chronic
inflammation before they become cancer● Provide cancer treatment at a very earlystage, rather than an advanced stage

risk of cancer development could be accurately predicted, their very early detection andtreatment before they became cancer can be achieved. If they could be cured by simple
treatment (in comparison with that required for advanced cancer), it reliefs the burden
on the patient. Developing mathematical models for accurately recapitulating thechanges in the body and conducting large-scale cohort studies will further increase thisaccuracy of the biomarker(s) identified in our study. Our goal is to achieve a cancer-freesociety by developing a universal model to predict the risk that abnormal cells will
become cancer in the body.

● Construct mathematical models predicting the transformationfrom chronic inflammation to cancer● Develop highly sensitive devices to detect the causes ofinflammation and precancerous cells at a very early stage● Develop very early-stage cancer treatments, including cancer

immunotherapy, targeting precancerous cells

TODAY

2030
TARGET

2040
BREAKTHROUGHNISHIKAWA Hiroyoshi Project Manager
Professor, Graduate School of Medicine, Nagoya University

Nishikawa decided to study tumor immunology in graduate school for developing new cancer therapies
considering the poor effectiveness of chemotherapy for patients with advanced cancer when he was a
medical resident. He obtained his Ph.D. degree by the identificaiton of the regulatory mechanism of theimmune response to cancer, and went on to study at the Memorial Sloan Kettering Cancer Center, theworld’s main center of cancer immunology research. He took up appointments at the National Cancer
Center Research Institute in 2015 and simultaneously at Nagoya University in 2016, where he isengaged in research for studying the mechanisms that regulate “immune tolerance” and“immunosurveillance” against self and non-self, respectively, via deeply considering the diversity ofcancer, paticularly in humans. He is a world leader in studying the mechanism by which the genetic

NISHIKAWA Hiroyoshi

alterations in cancer cells directly modulate the immune system to form an immunosuppressed tumor
environment, thereby establishing innovative concepts and strategies for cancer treatment.

Editor/Publisher

Yomiuri Shimbun Bldg., 1-7-1 Otemachi, Chiyoda-ku, Tokyo 100-0004, Japanmoonshot@amed.go.jp
March 2024 (1st edition)