Introduction: Grandmother's Prayer
As a species, we are living much longer than we used to.
But it's not a much better life.
Never.
Over the past century, the number of years we live has increased, but the number of years we can call life has not increased.
In any case, the quality of life itself has not increased much.
So when most of us think about whether we'll live to be 100, we still think, "I hope not."
Because we've seen what those last few decades have been like, and for most people, most of the time, it doesn't look very appealing.
Oxygen respirators and all kinds of medications.
Hip fracture and diapers.
Chemotherapy and radiation therapy.
Surgery, surgery again.
And medical expenses.
Oh my gosh, those medical bills are outrageous.
We die slowly and painfully.
People in wealthy countries sometimes suffer from various diseases for more than a decade before dying.
We think this is normal.
(…)
But what if it didn't have to be that way? What if you could live younger and longer? What if you could live decades, not just years? What if your final years didn't seem so different from the years that came before? And what if, by saving yourself, you could also save the world?
I'll probably never be six again, but what about twenty-six or thirty-six?
What if we could play like children, living our lives more fully, without worrying that we'd soon have to move on to the things we "should" do as adults? What if we didn't have to compress all the things we're supposed to cram into our teens? What if we didn't have to stress so much in our twenties? What if we didn't feel middle-aged in our thirties or forties? What if we wanted to start anew in our fifties and couldn't find a single reason why we shouldn't? What if, instead of fretfully thinking about leaving a mark in our sixties, we started making new ones?
What if I told you that you wouldn't have to worry about time passing? And soon? In fact, very soon? You wouldn't have to worry about that anymore?
That's exactly what I'm trying to say.

--- pp.28~29

Chapter 1: Long Live the Primitive Creatures
The 'information theory of aging' starts from the primitive survival circuits we inherited from our distant ancestors.
As you might expect, this circuit has evolved over time.
For example, mammals do not have just two genes that constitute the survival circuitry that first emerged in Magna superstes.
Scientists have identified at least 22 such genes in our genome.
Most of my colleagues call these “longevity genes.”
Because in many organisms, these have been shown to increase average and maximum lifespan.
But these genes don't just make you live longer; they make you healthier.
So these can also be called “vitality genes.”
These genes form a kind of surveillance network within the body that monitors what we eat, how much we exercise, and what time of day it is, and responds by secreting proteins and chemicals into the bloodstream, communicating between cells and organs.
When things are going badly, it tells us to stay still and hold our breath, and when things are going well, it tells us to grow quickly and reproduce.
We now know these genes, and we have already identified what many of them do.
Therefore, there is an opportunity to explore and exploit these genes through scientific discovery.
There is also an opportunity to imagine what potential these might hold and leverage them in different ways.
By using molecules in natural and creative ways, by employing simple and complex technologies, and by drawing on new and existing wisdom, we can identify these genes, tweak them in different ways, and even change them entirely.
The longevity gene I'm studying makes a protein called "sirtuin."
It is named after the SIR2 gene first discovered in yeast.
Mammals have seven sirtuin genes, SIRT1 to SIRT7, and sirtuin proteins are produced in almost every cell in the body.
When I began my research, sirtuins were virtually unknown to the scientific community.
This group of genes is currently at the forefront of medical research and drug development.

--- pp.72~73

Chapter 2: The Pianist in Confusion
It's worth taking a moment to pause here and consider how remarkable it is that essentially the same longevity genes are present in every living thing on Earth: trees, yeast, worms, whales, and humans.
All living things evolved from the same primordial life form, and so do we.
If you look at them under a microscope, you can see that they are all made of the same raw materials.
They all have the same survival circuits, intracellular connections that protect them when things get tough.
But this network is also the cause of our downfall. There are types of damage we cannot avoid, like breaks in our DNA strands.
Such damage overtaxes survival circuits and alters the cell's identity.
According to the 'information theory of aging,' we all suffer from epigenetic noise that causes aging.
However, each living creature ages at a different rate.
And there are creatures that seem to never age.
How can bowhead whales maintain their survival circuits without disrupting their epigenetic symphony? If pianists' skills decline, how can jellyfish restore their abilities?
These questions have guided my thinking as I consider where our research should go.
It may seem like a wild idea or a concept straight out of science fiction, but it is firmly rooted in research.
Moreover, the fact that some of our close relatives have learned to avoid aging supports this notion.
And if they can do it, so can we.

--- pp.126~127

Chapter 3: Blind Practice
As we go further into the future, death is no longer attributed to old age.
No one dies “of old age” anymore.
Over the past century, Western medicine has come to believe that there are more immediate causes of death than aging, and that identifying them is a pressing need.
In fact, over the past few decades we have become more discerning about the causes of death.
The World Health Organization's International Classification of Diseases, a list of diseases, symptoms, and causes of injury, had 161 entries when it was first published in 1893.
But now there are over 14,000, and in most places where death records are kept, doctors and public health officials use these codes to record the direct and underlying causes of disability and death.
And health officials and policymakers around the world use that data to inform public health decisions.
Generally, the more frequently a cause is listed on death certificates, the more vigilant society is to address that cause.
That's why heart disease, type 2 diabetes, and dementia are major research and medical concerns, while aging, the biggest cause of all these diseases, receives little attention.
Although aging is sometimes considered a fundamental factor in ending life, doctors never say that it is the direct cause of death.
Saying something like that risks provoking the anger of the official in charge.
It is likely that the certificate will be returned to the doctor asking for more specifics.
Moreover, there is a high possibility of being ridiculed by colleagues.
“The idea that people die of old age alone, without any disease, is nonsense,” David Gems, associate director of the Institute of Healthy Ageing at University College London and author of a report for the Royal Society’s “New Science of Ageing” conference, told Medical Daily in 2015.
But that misses the point.
The perspective that separates aging from disease obscures the truth about how we reach the end of life.
It is obviously important to know why we fall off cliffs.
But it's equally important to know what brought us to that precipice in the first place.
It is aging that takes us to the edge of that cliff.
In about a hundred years, we will all be on the edge of that precipice, dragged along by the hand of aging.

--- pp.141~142

Chapter 4: How to Live a Long and Healthy Life
The diet isn't a bad starting point.
It's actually a very good starting point.
Even the world's leading nutritionists disagree on what constitutes the "best" diet for Homo sapiens.
The reason is most likely because there is no such thing as the best diet.
Because people are so diverse, their diets may vary subtly, sometimes significantly.
But on the other hand, we are all similar enough to have many things in common when viewed broadly.
Eat more vegetables and less meat.
Eat less processed foods and more fresh foods.
This is something everyone knows.
It may be difficult to put into practice, though.
Why do so many people find this challenge so difficult to accept? A large part of it is because we've always assumed aging is an inevitable part of life.
Because we've all heard that aging is something that will inevitably happen to all of us, whether it comes a little earlier or a little later.
In the past, this was said about pneumonia, flu, tuberculosis, and gastrointestinal diseases.
In 1900, these four diseases accounted for about half of all deaths in the United States. If you lived long enough to contract one of them, you were almost certain that one of them would eventually take your life.
Today, it is extremely rare for people to die from tuberculosis or gastrointestinal diseases.
Deaths from pneumonia and flu have fallen to less than 10 percent of what they were a century ago.
And the majority of those who die are people weakened by old age.
What's changed? The system itself hasn't changed at all.
Thanks to advances in medicine, technological innovations, and better information that helps us improve our lifestyles, we no longer need to accept the notion that such diseases are “just the way they are.”
Likewise, we don't have to accept aging that way.
But even for those most directly exposed to the drugs and technologies that will enable longer, healthier lives in the coming decades, reaching optimal lifespan and healthspan will not be as easy as flipping a light switch.
There will always be good choices and bad choices.
And that choice starts with what we put into our bodies.
Also in 'What not to put in'.

--- pp.173~174

Chapter 5: Easy-to-Eat Pills
When you understand how cells actually work, you realize how amazing it is.
The problem with trying to convey this wonder in the classroom is that cells exist in four dimensions of space and time, moving at speeds and scales we humans cannot perceive or even imagine.
Seconds and millimeters are units that divide time and space very briefly.
But for enzymes, which are about 10 nanometers in size and vibrate 1,000 trillion times a second, a millimeter is the size of a continent and a second is more than a year.
Consider catalase, a common enzyme of average size that can detoxify 10,000 hydrogen peroxide molecules per second.
One million of these enzymes will fit inside an E. coli, and one million E. coli can fit on the head of a pin.
These numbers are beyond imagination.
I can't even imagine it.

A single cell contains 75,000 enzymes, like catalase, all bouncing around in a slightly salty sea of ​​cells.
At the nanoscale, water is gelatinous, and collisions between molecules are more violent than a Category 5 typhoon.
Molecules are pushed around at speeds of up to 1700 kilometers per hour.
Enzyme reactions are events that occur with a probability of one in a thousand, but at the nanoscale, this probability means that they can happen thousands of times in just one second.
Enough to sustain life.
I know it sounds chaotic when I say it like this, but chaos is necessary for order to emerge.
If there were no chaos, the molecules that need to come together to support life would not meet or merge.
(…)
If the chaos were to stop and our enzymes suddenly stopped doing what they were doing, we would die in seconds.
Life cannot exist without energy and cellular defense systems.
Magna Supertes could never have emerged from the dungeon, and would never have had descendants who could understand the words of this book.
So, at a fundamental level, life is pretty simple.
We exist by the grace of order created from chaos.
When we toast to life, we should actually toast to enzymes.
Studying life at this scale has taught us another important lesson.
Nobel Prize-winning physicist Richard Feynman expressed the lesson succinctly:
“Nothing has been discovered in biology so far that suggests the inevitability of death.
So I see death as never inevitable, and it's only a matter of time before biologists discover what brings us this misery.”
That's right.
There is no biological, chemical, or physical law that says life must end.
Of course, aging is the increase in entropy, the loss of information leading to disorder.
However, living things are not 'closed systems'.
Life can persist indefinitely as long as it can preserve vital biological information and absorb energy from somewhere in the universe.
This doesn't mean we can become immortal tomorrow.
Just as we couldn't fly straight to the moon on December 18, 1903.
Science advances by taking small steps and big steps, but always one step at a time.
Here's the amazing thing.
In fact, we have been taking the first steps since the days of Gilgamesh and Methuselah, or even since the days of Magna Supertes.
And over the past few hundred years, and perhaps even earlier, we have discovered ways to chemically control enzymes using molecules we call drugs.
We know how life works, and we have the tools to alter its operating patterns at the genetic and epigenetic levels, so we can build on this ancient wisdom.
And the easiest way to achieve the goal of extending healthy lifespan is to use a variety of drugs that are already known to affect human aging.

--- pp.218~221

Chapter 6: A Great Leap
When we first get the shot at age 30, there will be no change in the way our genes work.
However, when the aging effects begin to appear and be felt in your mid-40s, you will be given a safer switch, doxycycline, over a period of one month.
Then the reprogramming genes will be turned on.
In the meantime, you might want to drop a drop of blood into a home biomarker tracker or visit a doctor to make sure the system is working properly, but you don't have to.
After a month, your body will undergo a rejuvenation process as the Waddington Pebbles return to where they were when you were young.
Gray hair will disappear.
The wound will heal faster.
Wrinkles will disappear.
The organ will be regenerated.
Your brain will work faster, you will hear higher frequency sounds, and you will no longer need glasses to see menus.
You will feel young again.
You'll feel like you're 35 again, like the movie star Benjamin Button.
After that, you will feel like you are back to 30, and then 25.
But unlike Benjamin Button, you won't stop there.
Because I will stop administering the medication.
Then the adeno-associated virus will be turned off.
The Yamanakas will remain silent.
Biologically, physically and mentally you will be 20 years younger, but your knowledge, wisdom and memories will remain intact.
You will not just look younger, you will actually become younger again, and you will spend the next few decades without the aches and pains of middle age, and without worrying about cancer and heart disease.
After a few decades, when the gray hair starts to grow again, you will start taking medication again to start the rejuvenation process.
Moreover, given the pace at which biotechnology is advancing, and the speed at which we're learning how to manipulate the factors that reset our cells, we might be able to move beyond using viruses to simply taking a pill for a month.
Does this sound like science fiction? Like something from the distant future? Let me be clear: it's not.

--- pp.290~292

Chapter 7: The Age of Innovation
The barrier has fallen.
And it will continue to fall apart.
Next generations will inevitably see movie stars in their 60s and 70s speeding around on motorbikes, taking high-altitude jumps, and kicking high into the air.
Because 60 will be the new 40.
After that, 70 will become the new 40.
It will continue to die like that.
When will such a day come? It's no exaggeration to say that you, the reader of this book, are likely to benefit from this revolution.
You will look younger, act younger, and feel younger.
This is true for both body and mind.
You will live longer and be healthier during that extended period.
Of course, it is clear that any one technology can lead to a dead end.
However, not all technologies are likely to fail.
Each of these innovations in pharmaceuticals, precision medicine, emergency medicine, and public health will save lives, extending life by years.
By bringing all these technologies together, we are moving towards decades of healthier living.
Every new discovery opens up new possibilities.
Every minute we can shave off by making genetic sequencing faster and more accurate can help save lives.
Even if we don't extend our maximum lifespans by much, this era of innovation will undoubtedly allow us to live much longer and much healthier lives.
That doesn't mean that for many of us, that's generally the case.
It will be the same for all of us.

--- pp.356~357

Chapter 8: What Happens Next
Look around you.
What is truly “natural” about your current surroundings?
We have long since left behind a world in which Thomas Hobbes predicted in 1651 that the vast majority of mankind would have “no art, no writing, no society… and the worst of all, they would be in constant fear and danger of a violent death.”
If the kind of life Hobbes speaks of is truly natural, I have no interest in living a natural life, and I'd wager that you probably won't either.
So what is natural? To live a better life? To strive for a world with less fear, danger, and violence? We can certainly agree that the impulses that urge us are natural.
And it's clear that many of the adaptive traits that enable us to survive on Earth, including our wondrous survival circuits and the longevity genes that emerge from them, are the products of natural selection.
In other words, it is the result of billions of years of filtering out individuals who failed to stay silent when things were bad.
We have also accumulated a great deal of technology over the past 500,000 years.
It is natural for chimpanzees to poke termite nests with sticks, for birds to drop rocks to break mollusk shells, and for Japanese macaques to bathe in hot springs.
Humanity just happens to be better at learning technology and passing it on.
For the past 200 years, we have been inventing and utilizing a process called the scientific method.
It is a process that has promoted the development of learning.
So, according to this way of thinking, both culture and technology are “natural.”
Innovations that enable us to feed more people, control disease, and extend healthy lives are natural.
Cars and airplanes are like that.
Laptops and cell phones are like that.
Pets like dogs and cats are like that.
The bed we sleep in is like that.
That's what a hospital is like, where people take care of each other when they're sick.
All this is natural for creatures who have long since surpassed the human population that could barely survive in conditions that Hobbes described as “solitary, poor, miserable, brutish, and short.”
The only thing I see as unnatural—in the sense that it's something that has never happened in the history of our species—is accepting limitations on what we can and cannot do to improve our lives.
We have always pushed the boundaries of what we perceive.
In fact, biologically we are driven to do so.
Sustaining vitality is simply an extension of this process.
It is clear that there are consequences, challenges, and risks involved.
One of them is population growth.
But possibility is not inevitability.
As a species, we are pressured to innovate our responses.
So the question isn't whether our planet's natural or unnatural bounty can support 8 billion people, 16 billion people, or 20 billion people.
That point is irrelevant.
The question is whether humanity can continue to develop technologies that will keep us ahead of the growing population and make the Earth a better place for all living things.
Can we do it?
Absolutely.
And the 20th century is proof of that.

--- pp.404~406

Chapter 9 The Path We Must Take
If significantly extended vitality is a certainty in our future, what would you like the world to be like?
Would you be okay with a future where the rich live far longer than the poor, and thus become increasingly wealthy with each passing year? Would you want to live in a world where an ever-growing population drains the planet's last remaining resources, making the world increasingly uninhabitable?
Then there is nothing for you to do.
If you just keep doing what you're doing now, that future will come.
In fact, it probably doesn't matter whether it extends human lifespan or not.
All you have to do is sit back, relax, and watch the world burn.
But there is another possible future.
A future where increased youth becomes a beacon for universal prosperity, sustainability, and greater human dignity.
A future where vast resources are released from a medical industrial complex built on defeating diseases individually, creating enormous opportunities to address other challenges.
A future where those who have lived on this planet for a long time are respected for their knowledge and skilled craftsmanship.
It is a future where Good Samaritanism spreads throughout the world.
Again, this future is something we must fight for.
Because it is never guaranteed.

--- pp.437~438

Going Out: Towards the 22nd Century
There are those who believe that people in our lab—and those doing the same work in labs around the world—are engaging in unnatural, even immoral, acts that alter the very meaning of human existence.
Such a view is based on a concept of human nature that could be said to be subjective at best, but more precisely, it is based on a concept of human nature that could be said to be blindly faithless.
I think that force was also at work behind the report Beyond Therapy: Biotechnology and the Pursuit of Happiness, submitted to the White House by the President's Commission on Bioethics in 2003.
The report issued an ominous warning about aging research, saying it goes against the "human grain" and the so-called ordered cycle of birth, marriage and death.
The committee raised the following question:
“If the average life expectancy at marriage were 80 or even 100 years old, rather than 50 as it is now, would we be less or more inclined to make the vow of ‘until death do us part’?” I would ask, conversely, this question.
What kind of unhappy marriage do you imagine you're supposed to have that prompts people to ask such questions? I'd gladly spend another 50 years with my wife.
The committee argued that:
“Aging is a process that mediates the course of our lives and shapes our sense of time,” he said, warning that without it, “our lives could be thrown into chaos.”
Of course, our so-called natural lifespan means that most of our ancestors never lived to the age of graying hair or wrinkles, and being eaten by carnivores was a perfectly normal way to end their lives.
If you want to stick to that life, I won't stop you.
The committee asked:
“Are we not deluding ourselves by breaking free from the natural contours and constraints of life (our frailty and finitude) that serve as a lens through which to view the broader landscape that can give life all its coherence and enduring meaning?”
If we truly believed that aging was a prerequisite for a meaningful life, we would never treat broken bones, give polio vaccinations, or advise women to get enough calcium and exercise to prevent osteoporosis.
Of course, I know very well that I shouldn't get upset and bring up these issues unnecessarily.
After all, it's a lesson as old as the history of science.
Ask Galileo what happens when you “disturb the natural order of things.”
(…) In the years since the report came out, aging research has been stigmatized as a fight against humanity rather than a fight against disease.
That's nonsense, and in my view, it's rather fatal nonsense.
(…) Try volunteering for a day at a nursing home.
Feed those who cannot chew.
Take their urine and feces.
Try giving him a bath.
Watch those who have difficulty remembering who they are and where they are.
After experiencing these things, you will agree with me that not fighting the problems of aging when you can is irresponsible and cruel.

--- pp.489~492