prolog

When I finally realized that what we were doing was futile, I was so frustrated that I left medicine and chose a completely different field.
But as various experiences since then have converged, my existing perspective on health and disease has fundamentally changed, and I returned to the medical field with a new approach and new hope.

This is why we come back to the falling egg dream.
In short, I finally realized that better egg reception wasn't the only way to solve this problem.
Instead, we had to try to stop someone from throwing eggs.
I had to climb to the top of the building, find that person, and figure out how to bring them down.

--- p.32~33

Chapter 1: The Long Game: Surviving in a World of Slow Death

Most of my patients understand this instinctively.
When they first come to see me, they usually claim, “I don’t want to live any longer,” if longevity means dragging on longer in a state of increasingly declining health.
Many of them watched their parents or grandparents live that life.
Alive but too old or debilitated to move.
They confess that they never want to reenact such an old and sick appearance.


It is at this point that I interrupt them.
I tell them that just because their parents lived long and difficult lives or unfortunately died young, it doesn't mean they have to live that way.
The past doesn't have to define the future.
Your longevity is more malleable than you think.


Life expectancy in 1900 was less than 50 years, and most people were likely to die from 'quick' causes such as various accidents, injuries, and infections.
Since then, slow death has replaced quick death.
Most people reading this book will likely die in their 70s or 80s, and almost all of them will die of 'slow' causes.


Unless you enjoy extremely risky activities like base jumping, motorcycle racing, or texting while driving, your chances of dying from what I call the "Four Horsemen disease" are overwhelmingly high.
These include heart disease, cancer, neurodegenerative diseases (dementia, Alzheimer's disease), and type 2 diabetes (and related metabolic disorders).
To achieve longevity—that is, to live longer and healthier lives—we must understand and confront the causes of this slow death.
--- p.42~43

My goal is to create a practical user manual for healthy longevity, a guide to help you live longer and healthier lives.
I want to give you the confidence that with enough time and effort, you can extend your lifespan by 10 years and your healthy lifespan by 20 years, and live 20 years younger than your peers.

But my intention here is not to tell you exactly what to do.
The idea is to help you learn how to think about how to do these things.
For me, this work has been a journey, a process of obsessive study and repetition, that began on the rocky beaches of Catalina Island.

More broadly, longevity demands a paradigm shift in medicine.
We must redirect our efforts toward preventing chronic diseases and improving our healthy life expectancy.
Don't wait until you get sick or your cognitive and physical functions have already declined; take action now.
This is not 'preventive medicine'.
It is 'proactive medicine'.


I believe that this new medicine can not only transform individual lives, but also alleviate the tremendous suffering our entire society is experiencing.
And this change doesn't happen automatically in medicine.
It only happens when the patient and doctor request it.


We need to change the way we approach medicine.
That way we can climb up on the roof and stop the eggs from falling.

--- p.57

Chapter 2: Medicine 3.0 is Coming: Personalized Medicine for the Era of Chronic Disease

This is why I believe we need to think about chronic disease, chronic disease management, and long-term health maintenance in a new way.
The goal of this new medicine, which I call "Medicine 3.0," is not to remove the tumor, stitch up the incision, hope the surgery went well, and then send you home.
Preventing tumors from appearing and spreading in the first place, avoiding the first heart attack, or preventing people from developing Alzheimer's disease—these are the goals of Medicine 3.0.
Our treatment, prevention, and detection strategies must adapt to the characteristics of these diseases, which have a long and slow prelude.

It is already clear that medicine in our time is changing rapidly.
Many experts have predicted that a dazzling new era of 'personalized medicine' and 'precision medicine' will dawn.
An era where healthcare is tailored to each of our individual needs, even tailored to our genes.
This is certainly a worthy goal.

It is clear that no two patients are exactly alike.
This is true even if two patients appear to have the same respiratory disease.
A treatment that works for one patient may be useless for another.
It could be that your immune system is reacting differently, or that you are infected with a virus rather than a bacteria.
Even today, it is extremely difficult to distinguish these differences, leading to millions of prescriptions for ineffective antibiotics.

--- p.73~74

Perhaps this is the most crucial difference between Medicine 2.0 and Medicine 3.0. In Medicine 2.0, you are merely a somewhat passive passenger on a ship.
Medicine 3.0 demands much more from you.
You must be well informed, have some medical knowledge, have clear goals, and be able to recognize the nature of the risks.
You must be willing to change ingrained habits, embrace new challenges, and venture out of your comfort zone when necessary.
You are never passive, you are always involved.
Don't ignore problems until it's too late, and face them head on, even if they are uncomfortable or scary.
You literally jump right into the game.
And make important decisions.

In this scenario, you are no longer a passenger on the ship.
You are the captain of this ship.
--- p.83~84

Chapter 3: Goals, Strategies, and Tactics: A Roadmap for Mindset and Lifestyle Change

This curve represents the ideal trajectory.
This orbit is exactly what we want.
Instead of beginning a gradual decline in middle age, overall health expectancy remains the same or improves well into your 50s.
At 55, or even 65, you will be stronger and healthier than you were at 45, and you will maintain a healthy body and sharp cognitive skills well into your 70s, 80s, and even beyond.
You will look 10, no, 20 years younger than the age on your passport.
This curve has much more space underneath, which means a longer and better life.
A life where you spend more time with your family, pursue your passions, travel, and continue to do meaningful work.
Moreover, when it finally begins to decline, the decline is steep and relatively short.
This is called 'squaring the longevity curve'.

According to this scenario, we live longer.
And live longer and better.
We live longer than expected and exceed society's expectations for our later years.
Instead of a decade of chaos, we enjoy a "bonus decade"—or "bonus decades"—when we thrive in all dimensions.
This is our goal.
It's about delaying death and making the most of the extra years of life you've had.
At this point, the rest of our lives will become enjoyable rather than boring.
--- p.91

The key difference between Medicine 2.0 and Medicine 3.0 has to do with when and how we apply our tactics.
Typically, Medicine 2.0 only intervenes when acute problems arise, such as infections or fractures, with short-term solutions to the immediate problem.
In Medicine 3.0, tactics must be intertwined with everyday life.
You literally have to eat, breathe, and sleep with the tactics.

Medicine 2.0 relies largely on two types of tactics: procedures (such as surgery) and drug therapy.
On the other hand, the tactics of Medicine 3.0 are largely divided into five areas.
Exercise, nutrition, sleep, emotional health, and exogenous molecules.
Exogenous molecules include drugs, hormones, and nutritional supplements.

--- p.102

Chapter 4: The Secret of Centenarians: The Secret to Getting Healthier as You Age

The goal of Medicine 3.0 is to help people live a life path closer to, or even better than, a centenarian life.
Centenarians not only live longer, they live longer in good health.
This means that many of them will enjoy an extra 10 years, or even 20 or 30 years.
Even at 90 years old, they are sometimes healthier than the average person in their 60s.
And when it comes to aging, the period is usually short.

We all want to live longer, maintain our physical functions, and be free of chronic diseases, and then die with a shorter illness at the end of our lives.


The difference is that while most centenarians seem to have achieved longevity and good health almost by accident, thanks to genes and luck, most of us have to work to achieve the same.
Here we move on to the next two questions:

How do centenarians delay or avoid chronic diseases? And how can we do the same?
--- p.127~128

To sum up, I believe the secret of centenarians can be summed up in one word.
It is ‘resilience’.
Centenarians can resist and avoid cancer and cardiovascular disease even after smoking for decades.
They can maintain ideal metabolic health even with poor eating habits.
And they resist cognitive and physical aging long after their peers have succumbed to it.
--- p.137~138

Chapter 5: In Search of Longevity Elixirs: Drugs That Help You Eat Less and Live Longer

When the National Institute on Aging tested resveratrol in the same rigorous way as rapamycin as part of a program to screen promising anti-aging drugs, it did not produce similar lifespan extension results in various groups of normal mice.

The same goes for overhyped supplements like nicotinamide riboside, or NR.
This substance has also been consistently shown to have no life-extending effect in mouse experiments.
Of course, there is absolutely no data showing that these supplements extend lifespan or improve health in humans.

In contrast, studies conducted since 2009 have continued to reaffirm that rapamycin reliably extends lifespan in mice.
This was also shown to be the case in yeast and fruit flies.
The same effect was observed when mTOR activity was reduced by genetic manipulation.
Therefore, any rational person might conclude that it would be beneficial to inhibit mTOR activity, at least temporarily.
Therefore, it is possible that rapamycin, an mTOR inhibitor, may be a life-extending drug.
--- p.146

Chapter 6: Diabetes and the Metabolic Health Crisis: Can Our Ancient Genes Cope with the Modern Diet?

Although cirrhosis is a serious disease, it is not the only end point that concerns me here.
So I'm more concerned about nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.
And you should too.
Because these two conditions represent the tip of the iceberg of a global epidemic of metabolic disorders, ranging from insulin resistance to type 2 diabetes.
Type 2 diabetes is a distinct disease that is academically very clearly defined by blood sugar levels.
However, I see this as the last stop on a railway line that passes through several stations including hyperinsulinemia, prediabetes, and non-alcoholic fatty liver disease/non-alcoholic steatohepatitis.
If you're anywhere along this path, even if you're in the early stages of nonalcoholic fatty liver disease, you're likely to suffer from one or more of the four horsemen diseases: cardiovascular disease, cancer, diabetes, and Alzheimer's disease.
As we will discuss in the next few chapters, metabolic dysfunction dramatically increases the risk of all of these diseases.
Therefore, if you do not address the metabolic dysfunction first, you cannot fight the four knight diseases.

--- p.171

Gerald Riven, who passed away in 2018 at the age of 89, would have agreed.
He had to fight for decades to get his claim that insulin resistance is the primary cause of type 2 diabetes accepted.
It is now a widely accepted concept.
However, diabetes is only one of the risks that insulin resistance poses.
Studies have shown that insulin resistance significantly increases the risk of diseases such as cancer (up to 12 times), Alzheimer's disease (5 times), and cardiovascular disease mortality (almost 6 times).
All of this underscores that treating, or even preventing, metabolic dysfunction is a cornerstone of my approach to longevity.
--- p.196~197

Chapter 7: When Heart Disease Strikes: Fighting the Deadliest Killer on Earth

Our total cholesterol, the first number people usually bring up when talking about heart disease, actually has a little more to do with cardiovascular risk than eye color.

--- p.207

The final myth we must confront is the notion that cardiovascular disease occurs primarily in the "older" population, and therefore there is no need to worry about prevention in your 20s, 30s, or even 40s.
This is not true.
I'll never forget the quiz Alan Snyderman threw out while we were having dinner at the Dallas airport in 2014.
“Do you know what percentage of people under 65 have a heart attack?” I guessed it would be high, one in four, but that was way too low.
Fully half of the men and one-third of the women experienced some type of major acute cardiovascular event, such as a heart attack, stroke, stent or other transplant, before age 65.
A quarter of men who experienced this did so before the age of 54.

However, although this incident itself may seem to have occurred suddenly, it is likely that the problem has been going on for many years.
Atherosclerosis is a disease that progresses slowly and insidiously, which is why I am so actively engaged in this issue.
The risk of such 'events' increases sharply in the later years of life.
However, some scientists believe that the processes underlying this event begin in late adolescence, or even in the early teens.
This risk accumulates over a lifetime, and time is a key factor.
Therefore, it is crucial to understand how heart disease develops and progresses so that strategies can be developed to attempt to slow or halt its progression.

--- p.211

Chapter 8: Cancer, Unleashed Cells: A New Approach to Combating the Murderous Tumor

After 50 years of fighting cancer, it seems clear that no single 'cure' is likely.
Rather, the most hope seems to lie in finding better ways to attack cancer on all three fronts: prevention, more targeted and effective treatments, and comprehensive and accurate early detection.

--- p.250~251

It's unlikely that some miraculous breakthrough will occur in my lifetime, where we discover a way to completely prevent or "cure" cancer.
Therefore, until such a thing becomes possible, we must focus much more effort on detecting cancers early so that appropriate therapies can be targeted when individual cancers are at their most vulnerable stages.


If the first rule of cancer treatment is “don’t get cancer,” the second rule is “catch it as soon as possible.”


This is why I advocate early detection.
It is a simple truth that it is much easier to treat smaller tumors with fewer mutations than to wait for the cancer to progress and develop mutations that allow it to evade treatment.
The only way to catch cancer early is through active screening.

--- p.298

Chapter 9: Dementia, Memory, and Self-Loss: How to Beat Neurodegenerative Diseases Like Alzheimer's

Another thing I tried to emphasize to Stephanie was that time was on her side.
Alzheimer's disease rarely progresses to the point where it is clinically diagnosed until about age 65, even in people with a paired e4.
So, we have about 25 years to use the tools available today to try to prevent or slow the spread of this terrible disease.
In the meantime, researchers may come up with more effective treatments.
Stephanie's case was a classic asymmetrical situation, one where doing nothing was actually the riskiest course of action.
--- p.306

1.
What's good for your heart is good for your brain.
Vascular health (low apoB levels, low inflammation, low oxidative stress) is crucial for brain health.

2.
What's good for your liver (and pancreas) is also good for your brain.
Metabolic health is crucial to brain health.

3.
Time is of the essence.
We need to think about prevention earlier, and those who are genetically disadvantaged should start taking preventive measures even earlier.
Cardiovascular disease is a very long battle.


4.
The most powerful tool to prevent cognitive decline is exercise.
We've covered a lot of diet and metabolism, but exercise appears to play a multifaceted (vascular, metabolic) role in preserving brain health.
As we'll discuss in more detail in Part 3, exercise—lots of exercise—is a cornerstone of any Alzheimer's disease prevention program.

--- p.344

Chapter 10: Thinking Tactically: Building a Framework with Principles That Work for You

Medicine 3.0 sees five strategic areas we can attack to improve someone's health.
The first is ‘exercise’.
I believe exercise is the most powerful area for both longevity and health span.
Of course, exercise is not just one thing.
So I'm going to break down the workout into aerobic efficiency, VO2 max, strength, and stability.
The second is ‘diet’ or ‘nutrition’.
I prefer to call it 'nutritional biochemistry'.
The third area is ‘sleep’.
Medicine 2.0 is an area that was underestimated until relatively recently.
The fourth area includes a set of tools to manage and improve 'emotional health'.
The final fifth area is the various drugs, nutritional supplements, and hormones that doctors learn about in medical school and beyond.
I would like to lump these together and call them 'exogenous molecules'.
It means a molecule brought in from outside the body.

This section will not deal much with exogenous molecules beyond those already specifically mentioned (lipid-lowering agents, rapamycin, and metformin, a diabetes drug currently in clinical trials for its potential longevity benefits).
Instead, I want to focus on four other areas.
These are areas that are virtually not covered at all in medical school or residency programs, and are not even mentioned at all.
We have learned virtually nothing about exercise, nutrition, sleep, and emotional health.
This situation seems to be slowly changing.

--- p.350~351

Chapter 11 Exercise: The Most Powerful Longevity Elixir

If you read this book and want to develop just one new habit, it should be in the area of ​​exercise.
If you're currently exercising, you'll likely want to rethink and modify your exercise program.
And if you're not currently exercising, know that you're not alone.
Because 77 percent of the American population does.
Now is the time for change.
Right now.

Even exercising a little bit every day is better than not exercising at all.
Going from no exercise to just 90 minutes of exercise a week can reduce your risk of death from all causes by 14 percent.
It is very difficult to find a drug that can have this effect.

--- p.362

To follow in Laraine's footsteps, we need to stop doing pointless exercise out of obligation, like hitting the elliptical during lunch.
We can do better.
I recommend starting your exercise routine with a very specific goal in mind: “I’m going to be a great centenarian.”
When my patients tell me they're more interested in being a great 50-year-old than a centenarian decathlete, I respond:
“Just as an archer who trains to hit a 100-meter target will be more accurate at hitting a 50-meter target, setting a trajectory aimed at reaching 100 (or 90, or 80) is the best way to reach a great 50.” If we set our sights on the centenarian decathlon, we will be able to do well in 10 years, and then another 10.

I now train for the decathlon, a centenarian sport, with the same passion I once had for a specific sport like cycling, swimming, or boxing.
Rather than trying to be very good at one thing, try to be pretty good at everything.
As centenarian decathletes, we train not for one sport, but to become a completely different type of athlete.
He is the 'athlete of life'.
--- p.387

Chapter 12: Mastering the Basics of Exercise: How to Prepare for the Centenarian Decathlon

We plan to optimize our exercise routine based on the principles of longevity.
What combination of approaches can help us delay the onset of chronic disease and death while maximizing our healthy lifespan?

This question is more complex than how to lower your risk of cardiovascular disease.
Because there are more variables and more choices within each variable.
It's closer to a three-dimensional problem than a one-dimensional problem.
The three dimensions we want to optimize for fitness are cardiorespiratory fitness (aerobic endurance and efficiency), strength, and stability.
These three things are necessary to maintain health and fitness as we age (and, as we've seen, to extend our lifespan).
However, cardiorespiratory fitness and strength are much more nuanced than most people realize, and stability is even less understood.
--- p.390

I think of strength training as a kind of retirement pension.
We want to reach old age with enough muscle (and bone density) 'pension' to protect us from injury and allow us to continue the activities we enjoy.
It's like wanting to retire with enough money saved to live off of for the rest of your life.
Instead of scraping together what little money you have left in your bank account in your 50s and begging the stock market gods for help, it's far better to save, invest, and plan ahead so you can accumulate money little by little over several decades.
Like investing, strength training is cumulative, and the benefits compound.
The more you save early, the more you will benefit in the long run.

--- p.420

Chapter 13: Training for Safety: How to Prevent Injuries and Chronic Pain

The lesson I've learned is that no amount of cardio or strength training will help if you get injured and have to stop exercising for months—or even forever.
A study of people who suffered injuries while playing sports in college found that their quality of life continued to decline into middle age.
Injuries can have lasting effects not only physically but also psychologically for decades.
Having struggled with injuries for so long, I've come to realize how important the ability to maintain physical function is to my overall quality of life.

All of these research findings and my own experience support the first commandment of the movement I advocate:
“First, never harm yourself.”

How can we keep this commandment? I believe "stability" is the key.
But this also requires a change in mindset.
We need to overcome the mindset that we have to burn out every time we go to the gym.
In other words, you need to break free from the obsession that you have to rotate through all exercises, lifting the heaviest weights and doing the most reps every day.
As I've come to realize, pushing yourself like that without stability almost inevitably leads to injury.
If you keep trying to burn yourself out, you'll likely end up relying on your body's own "tricks," on deeply ingrained but potentially dangerous movement patterns.

We need to change our approach.
We need to focus on doing exercises correctly, cultivating safe and ideal movement patterns that allow the body to function as it was originally designed and reduce the risk of injury.
It's better to be smart than to work too hard.

--- p.433~434

The theory behind the DNS movement is that the series of movements a child makes as they learn to walk are not random or accidental, but rather part of a core neuromuscular developmental program that determines our ability to move correctly.
As we go through this series of movements, our brain learns to control our body and develop ideal patterns of movement.

( ··· ) The researchers realized that when we grow up, healthy people go through virtually the opposite process.
In other words, we lose these natural, healthy, and almost ingrained movement patterns.

Our youngest son, Airton, can sit with his knees bent so deeply that his little bottom practically touches the floor, while maintaining perfect balance and strength.
The perfect full squat, ass-to-grass squat, perfect hip flexion.
I am amazed every time I see it.
This is a completely priceless attitude.

--- p.442

Chapter 14: Nutrition, How to Eat Well: Beyond Diet to Nutritional Biochemistry

Instead of diet, we should talk about 'nutritional biochemistry'.
Then, we will leave the world of ideology and religion—and above all, emotions—and firmly return to the world of science.
We might think of this new approach as 'Nutrition 3.0'.
A nutrition approach that is scientifically rigorous, highly personalized, and (as we'll see later) based on feedback and data, not ideology and labels.
It's not to tell you what to eat.
To find out what's right for your body and goals.
Equally important is whether you can maintain that eating habit.

--- p.480

Chapter 15: Applying Nutritional Biochemistry: Finding the Diet That's Right for You

The standard American diet disrupts the body's metabolic balance.
It puts a huge strain on our ability to regulate blood sugar levels and causes us to store fat when we should be using it.
According to the U.S. Department of Agriculture, the main source of calories consumed by Americans comes from a category called "grain-based desserts," such as pies, cakes, and cookies.
These are the 'food groups' we eat the most.
If you eat a lot of grain-based desserts at places like cheesecake shops, your blood sugar levels will spike.
And as we saw before, if this continues to happen, it will soon become impossible to safely process all those calories.
The standard American diet is essentially at war with our metabolic health, and given enough time, most of us will lose this war.

--- p.502

Ultimately, the best nutrition plan is one that you can stick to.
How we utilize the three diets - calorie restriction, food restriction, and time restriction - is up to each of us.
Ideally, the plan would reduce the risk of the four most common diseases or conditions while improving or maintaining all the parameters we care about—not just blood sugar and insulin levels, but also muscle mass, fat mass, and even body weight.
Our nutritional goals will vary depending on our individual risk profile.
Are metabolic dysfunctions associated with a higher risk of cardiovascular disease? There's no one-size-fits-all answer.
Each person must find their own balance, the approach that works best for them.

--- p.563

Chapter 16: Improving Sleep Quality and Quantity: How to Love Sleep, the Brain's Best Medicine

Sleep is important for your body, but it may be even more important for your brain.
Good sleep, both in terms of quantity and quality, is crucial for our cognitive function, memory, and even emotional balance.
After a good night's sleep, we feel much more refreshed in every way.
Even when we are unconscious, our brains are still working, processing thoughts, memories, and emotions (hence our dreams).
Furthermore, sleep cleans the brain in a similar way that a city cleans its streets.
There is also growing evidence that good sleep is essential for preserving cognitive function and preventing Alzheimer's disease as we age.

--- p.569

The key point here is that a good night's sleep depends to some extent on how well you spend your daytime wakefulness.
This includes exercise, outdoor activities, mindful eating (including avoiding late-night snacking), minimal or no drinking, proper stress management, and knowing where to draw the appropriate line for stressors, including work.
--- p.602

Chapter 17: Caring for Your Emotional Health: The Cost and Lessons of Neglecting Your Emotional Health

These types of problems are much more widespread than suicide rates suggest.
It robs us of the joy of focusing on our health, our lives, and our relationships, and instead of living, it leaves us waiting for death.
This is why I believe that emotional health represents the most important factor in a healthy lifespan.
Longevity is virtually worthless without some degree of happiness, fulfillment, and connection with people.
And misery and unhappiness can damage your physical health just as surely as cancer, heart disease, neurodegenerative diseases, and fractures.

--- p.617

For example, the disease-based model that Medicine 2.0 primarily uses to address and solve problems such as infections and acute diseases is as follows.
The idea is to treat the symptoms and then send the patient home.
If the situation is more severe, as in my case, the patient is sent to a place like a recovery bridge for two weeks and then sent home.
Hurray, problem solved.

One reason this approach hasn't been very successful in the field of psychology is that mental health and emotional health are not the same thing.
Mental health includes medical conditions such as clinical depression and schizophrenia.
These are cases that are complex and difficult to treat, but present recognizable symptoms.
On the other hand, here we are focusing more on 'emotional health'.
Emotional health includes mental health, but it is much broader.
And it is more difficult to categorize and assign disease codes.
Emotional health has more to do with regulating emotions and managing relationships.
Although I did not have a mental illness, I had serious emotional health problems that interfered with my ability to live a happy and well-adjusted life.
As a result, my life itself could be at risk.
Medicine 2.0 is not well suited to this situation.

Taking care of our emotional health requires a paradigm shift, similar to moving from Medicine 2.0 to Medicine 3.0.
--- p.628

Epilogue

Eric told me.


“I think people grow old when they stop thinking about the future.
If you want to know people's real age, listen to what they say.
If they talk about old times and only talk about what happened in the past, they are old.
If you talk about your dreams and aspirations, you are still looking into the future.
“Because you’re young.”

This is the secret to staying young as you age.

--- p.665