Lifespan: The Revolutionary Science of Why We Age—and Why We Don't Have To

by David A. Sinclair

By injecting the mice with stem cells inactivated by radiation and later adding a booster shot like those humans use for tetanus, hepatitis B, and whooping cough, the stem cells primed the immune system to attack cancers that normally would be invisible to the immune system.8 Other immuno-oncological approaches are making even greater strides.

Therapies such as PD-1 and PD-L1 inhibitors, which expose cancer cells so they can be killed, and chimeric antigen receptors T-cell (CAR-T) therapies, which modify the patient’s own immune T-cells and reinject them to go kill cancer cells, are saving lives of people who, just a few years before, have been told to go home and make funeral arrangements.

To end aging as we know it, we need to find three more things that Shannon knew were essential for a signal to be restored even if it is obscured by noise: An “observer” who records the original data The original “correction data” And a “correcting device” to restore the original signal I believe we may have finally found the biological correcting device.

The ethics of the technology become more difficult, though, if reprogramming becomes safe enough to use in a way that is preventive. At what age should it be given? Does a disease have to appear before an antibiotic activator of reprogramming is prescribed? If mainstream doctors refuse to help, will people head overseas? If the technology could significantly cut health care costs, should it be mandated?

Should every human have a choice to suffer from aging? Or should that choice be made, as vaccine decisions are in most cases, for the good of both individuals and humankind? Will those who elect to be rejuvenated still have to pay for those who have decided not to? Is it morally wrong not to do so, knowing you will prematurely become a burden on family members?

As these technologies become commonplace and parents ponder how to get the biggest bang for the buck, how long will it be before another rogue scientist teams up with the world’s most driven helicopter parent to create a genetically modified family with the capacity to resist the effects of aging? It may not be long at all.

Most doctors, he said, still rely on early-twentieth-century technology to diagnose and treat life-threatening diseases. Take a swab and grow it in a petri dish. Bang the knee and wait for a kick. Breathe in, breathe out. Look to the left and cough.

But Boguski believes there is hope in a new way of doing medicine. A better way. A way that uses new technologies, many that are already here but simply not being utilized to their fullest potential, to refocus our medical system on individuals—upending centuries of deeply entrenched medical culture and philosophy. He coined the term precision medicine to describe the promise of next-generation health monitoring, genome sequencing, and analytics for treating patients based on personal data, not diagnostic manuals.

But for millions of people like Lawan, these advances cannot come soon enough. When her family sought a second opinion in the form of precision DNA sequencing of her lung tumor biopsy, the totality of the danger she was in became crystal clear. Lawan did have an aggressive cancer but not the kind of cancer for which she was being treated. She didn’t have lung cancer; she had a solid form of leukemia growing in her lung.

In the vast majority of cases in which cancer is found where it was found in Lawan’s body, it is indeed lung cancer. But now that we can detect the genetic signature of specific forms of cancer, using the place where you find the cancer as the only guide for what treatment to use is as ridiculous as categorizing an animal species based on where you’ve located it. It is like saying a whale is a fish because they both live in water.

That’s the idea behind one of the cancer-fighting innovations we discussed earlier, CAR T-cell therapy, in which doctors remove immune system cells from a patient’s blood and add a gene that allows the cells to bind to proteins on the patient’s tumor. Grown en masse in a lab and then reinfused into the patient’s body, the CAR T-cells go to work, hunting down cancer cells and killing them by using the body’s own defenses.

Through sequencing, we can even see what kinds of bacteria have managed to make their way into a tumor. Bacteria, it turns out, can protect tumors from anticancer drugs. Using genomics, we can identify which bacteria are present and predict which antibiotics will work against those single-celled tumor protectors.

If you accept that this is simply the way we care for people—and that it usually produces the right results—you could call this an understandable medical approach. But if you picture your own mother accidentally receiving a cancer treatment she doesn’t need while the medicine that will save her life sits on a shelf nearby, you’ll probably come to a different conclusion about what is, in fact, “understandable.” The hardworking, ethical doctors, nurses, and medical professionals who go to war with death every day, while navigating the overarching standard-of-care stipulations of governmental programs and insurance companies, should never be expected to be perfect. But we can prevent a lot of unnecessary deaths by giving medical staff more information, just as Lawan’s doctors were able to get her onto a new treatment regimen once they better understood what they were dealing with.

There are 3.234 billion base pairs, or letters, in the human genome. In 1990, when the Human Genome Project was launched, it cost about $10 to read just one letter in the genome, an A, G, C, or T. The entire project took ten years, thousands of scientists, and cost a few billion dollars. And that was for one genome. Today, I can read an entire human genome of 25,000 genes in a few days for less than a hundred dollars on a candy bar–sized DNA sequencer called a MinION that I plug into my laptop. And that’s for a fairly complete readout of a human genome, plus the DNA methyl marks that tell you your biological age.

But those aren’t the only questions that our DNA can answer. Increasingly, it can also tell you what foods to eat, what microbiomes to cultivate in your gut and on your skin, and what therapies will work best to ensure that you reach your maximum potential lifespan. And it can give you guidance for how to treat your body as the unique machine it is.

If females and males are in the same environment, in general, females will live longer. It’s a common theme throughout the animal kingdom. Scientists have tested whether it is the X chromosome or the ovary that is important. Using a genetic trick, they created mice with one or two Xs, with either ovaries or testes.9 Those with a double dose of the X lived longer, even if they had testes and especially if they didn’t, thus proving once and for all that female is the stronger sex.

In the future, a patient’s epigenetic age will also be determined and used to predict drug responses, a new field called pharmacoepigenetics. It’s a rapidly advancing technology but some pharmacogenetic tests can’t come soon enough.

Hopefully, there will be a pharmacogenetic test for this drug soon, as well as for many more. They are badly needed. We cannot keep prescribing medicines as though we all respond to them the same way, because we don’t.

This is the future. Eventually, every drug will be included in a huge and ever-expanding database of pharmacogenetic effects. It won’t be long before prescribing a drug without first knowing a patient’s genome will seem medieval.

The backlog could clear soon, thanks to technologies that give doctors the ability to conduct video home visits. Within a decade, using a device the size of a package of gum and possibly even disposable, it will be technically feasible to collect the samples your doctor needs at home, plug the device into your computer, and look together at a readout of your metabolites and your genes.

Soon, we will no longer have to wait for tumors to grow so big and so heterogeneously mutated that their spread is no longer controllable. With a simple blood test, doctors will be able to scan for circulating cell-free DNA, or cfDNA, and diagnose cancers that would be impossible to spot without the aid of computer algorithms optimized by machine learning processes trained on thousands of cancer patient samples. These circulating genetic clues will tell you not just if you have cancer but what kind of cancer you have and how to kill it. They will even tell you where in your body an otherwise undetectable tumor is growing, since the genetic (and epigenetic) signatures of tumors in one part of the body can be vastly different from those from other parts.

All of this means we’re on the way to a fundamental shift in the way we search for, diagnose, and treat disease. Our flawed, symptom-first approach to medicine is about to change. We’re going to get ahead of symptoms. Way ahead. We’re even going to get ahead of “feeling bad.” Many diseases, after all, are genetically detectable long before they are symptomatic. In the very near future, proactive personal DNA scanning is going to be as routine as brushing our teeth. Doctors will find themselves saying the words “I just wish we’d caught this earlier” less and less—and eventually not at all. But the coming age of genomics is just the start.

Rhonda Patrick, a longevity scientist turned health and fitness expert, has been using a continual blood glucose–sensing device to see what foods give her body a major sugar spike, something many of us believe is to be avoided if we are to give ourselves the greatest chance of a long life. She’s seen that, at least for her, white rice is bad and potatoes aren’t so bad. When I asked her what food had been the most surprising, she didn’t hesitate. “Grapes!” she exclaimed. “Avoid grapes.”

As I write this, I am wearing a regular-sized ring that is monitoring my heart rate, body temperature, and movements. It tells me each morning if I slept well, how much I dreamed, and how alert I will be during the day. Technology like this has been around for some time, I suppose, for people such as Bruce Wayne and James Bond. Now it costs a few hundred dollars and can be ordered by anyone online.23 Recently, my wife and eldest child came home with matching ear piercings, which got me thinking: there’s really no reason that an even smaller piece of body jewelry—particularly one that pierces the skin—couldn’t be used to track thousands of biomarkers. Every member of the family could be measured: grandparents, parents, and children. Even infants and four-legged family members will have monitors on them, because they are the ones who are least able to tell us what they are feeling.

The most critical daily decisions that affect how long we live are centered around the foods we eat. If your blood sugar is high at breakfast, you’ll know to avoid sugar in your morning coffee. If your body is low on iron at lunch, you’ll know it and can order a spinach salad to compensate. When you get home from work, if you’ve failed to go outside for your daily dose of vitamin D from the sun, you’ll know that, too, and you’ll be able to mix up a smoothie that will address the deficiency. If you’re on the road and you need X vitamin or Y mineral, you’ll know not only what you need but where to get it. Your personal virtual assistant—the same AI-driven being who answers your internet search queries and reminds you about your next meeting—will point you to the nearest restaurant that has what you need or offer to have it delivered by a drone to wherever you are. It could, quite literally, be dropped into your hands from the sky.

We already trade a tremendous amount of privacy for technological services. We do it all the time. We do it every time we start a bank account or sign up for a credit card. We do it often when we point our internet browsers to a new web page. We do it when we sign up for school. We do it when we get onto an airplane. And we do it—a lot—when we use our mobile phones. Have these been good trade-offs for everyone? That’s a matter of personal opinion, of course. But when most people imagine not being able to use a credit card, surf the web, sign up for school, travel by air, or use their phones and smart watches, they quickly conclude that the trade is tolerable.

Will people trade a little more privacy to stop a global disease pandemic? Sadly, probably not. The tragedy of the commons is that humans are not very good at taking personal action to solve collective problems. The trick to revolutionary change is finding ways to make self-interest align with the common good. For people to accept widespread biometric tracking in a way that could help us get ahead of fast-moving deadly viruses, they’ll need to be offered something they have a hard time seeing themselves without.

Now, having seen the changes on my dashboard, I cannot imagine living without it. Just as I now wonder how I ever managed to drive without a GPS, I wonder how I ever made decisions about what I should be eating and how much I should be exercising before I received regular updates from my biosensor ring and blood biomarker reports. Indeed, I am eager for the day in which the data about my health are processed in real time.

Today, many of my colleagues are just as optimistic as I am, even if they don’t admit it publicly. I’d wager that about a third of them take metformin or an NAD booster. A few of them even take low doses of rapamycin intermittently. International conferences specifically about longevity interventions are now held every few weeks, the participants not charlatans but renowned scientists from the world’s most prestigious universities and research centers. In these gatherings it is no longer unusual to hear chatter about how raising the average human lifespan by a decade, if not more, will change our world. Mind you, the debate is not about whether this will happen; it is about what we should do when it happens.

Kevin Kelly, the founding editor of Wired magazine, who has a better track record than most at predicting the future, has a golden rule: “Embrace things rather than try and fight them. Work with things rather than try and run from them or prohibit them.”

But as for the next century? And the next? It is not at all extravagant to expect that someday living to 150 will be standard. And if the Information Theory of Aging is sound, there may be no upward limit; we could potentially reset the epigenome in perpetuity

At least every couple of months, I get a call from a politician for an update on the latest developments in biology, medicine, or defense. Almost always we end up discussing what will happen to the economy as people live longer and longer. I tell him or her that there is simply no economic model for a world in which people live forty years or more past the time of traditional retirement. We literally have no data whatsoever on the work patterns, retirement arrangements, spending habits, health care needs, savings, and investments of large groups of people who live, quite healthily, well into their 100s.

Unless aging is designated a medical condition, initially only the wealthy will be able to afford many of these advances. The same will be true for the most advanced biotracking, DNA sequencing, and epigenome analyses to permit truly personalized health care. Eventually prices will come down, but unless governments act soon, there will be a period of major disparity between the very rich and the rest of the world.

To me, the only thing that seems unnatural—in that it has never happened in the history of our species—is to accept limitations on what we can and cannot do to improve our lives. We have always pushed against perceived boundaries; in fact, biology compels us to.

But the continual focus on the negative impacts the way we think about the state of our world today and in the future, which is likely why, when the global polling company YouGov asked people in nine developed nations, “All things considered, do you think the world is getting better or worse, or neither getting better nor worse?” only 18 percent of people believed that things were getting better.

“However, evidence suggests that if aging is delayed, all fatal and disabling disease risks would be lowered simultaneously.”

For the record, that’s precisely what I am suggesting will happen to the total disease burden as we slow and even reverse aging. The result will be an upgrade of the health care system as we know it. Treatments that once cost hundreds of thousands of dollars could be rendered obsolete by pills eventually costing pennies to make. People will spend the last days of their lives at home with their families instead of racking up huge bills in centers intended for nothing more than “aging in place.” The idea that we once spent trillions of dollars trying to eke out a few more weeks of life from people who were already teetering on the edge of death will be anathema.

The “peace dividend” we will receive from ending our long war on individual diseases will be huge.72 Over fifty years, Goldman estimated, the potential economic benefits of delayed aging would add u...

This army could be augmented by billions of additional women if they can be provided much longer windows of opportunity for pregnancy and parenting. Animal studies in my lab indicate that the window of female fertility could be extended by up to a decade. This is an exciting prospect because, in the United States, 43 percent of women step away from their careers for a period of time, almost always to shoulder the burden of child rearing. Many never return to work. As a woman’s lifespan and fertility lengthens, the consequences of taking a break will be seen as relatively minor. By this century’s end, we will almost certainly look back with sadness at the world we currently inhabit, in which so many people, particularly women, are forced to choose between parenting and career success.

But the small-sample Princeton experiment both followed and portended a lot of other research demonstrating that humans are a lot more humane when they’ve got more time.

The next question will be a rather grave one: “How do you die?” they’ll ask. And how we answer that question is going to be an important indicator of just how advanced we truly are. Right now, as my mother’s death exemplified, the way most of us die is barbaric. We go through a long period of decline, and we’ve come up with ways to extend that period of pain, grief, confusion, and fear so that we must experience even more pain, even more grief, even more confusion, and even more fear. The sorrow, sacrifice, and turmoil this creates for our families and friends are protracted and traumatic, so that when we finally pass on, it often comes as a relief to those who love us.

Here’s where things get really interesting: when I do this little survey and then tell the audience that they could retain their health no matter how many years they live, the numbers of those who say they’d like to live forever shoots way up. Almost everyone wants that. It turns out that most people aren’t afraid of losing their lives; they are afraid of losing their humanity.

In my mind, there are few sins so egregious as extending life without health. This is important. It does not matter if we can extend lifespans if we cannot extend healthspans to an equal extent. And so if we’re going to do the former, we have an absolute moral obligation to do the latter.