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

by David A. Sinclair

Instead of waiting for another year to see if the mice lived longer, Yuancheng suggested he use a mouse’s optic nerve as a way to test age reversal and rejuvenation. I was skeptical. “I’m not superoptimistic this will work,” I told him. “Optic nerves just don’t regenerate, unless you are a newborn.” The intricate network of cells and fibers that transmit nervous signals across our bodies is divided into two parts: the peripheral system and the central system. We’ve known for a long time that peripheral nerves, like those in our arms and legs, can grow back, albeit very, very slowly. The nerves of the central system, though—optic nerves and the nerves of the spinal cord—never grow back. Even those scientists who bucked convention, proposing novel therapies that could regenerate some aspect of the central system, have generally been circumspect about the potential for significant regrowth. Decades of work aimed at reversing glaucoma in the eye and spinal cord injury has had almost no positive momentum.

But on that day, things sure did seem to be working out. The image Yuancheng first texted to me looked like an orange, glowing jellyfish; its head was at the top, where the eye of the mouse sits, with long tentacles flowing down toward the brain. Two weeks earlier, Yuancheng and our collaborators had squeezed the optic nerve a few millimeters from the back of the eye with a set of tweezers, causing almost all the nerve cell axons, the tentacles, to die back toward the brain. They injected an orange fluorescent dye into the eye that is taken up by living neurons. So when Yuancheng took a microscope and looked below the crush site, there were no glowing nerves, just a mass of dead cell remnants.

adult cells in the body, even old nerves, can be reprogrammed to regain a youthful epigenome, the information to be young cannot all be lost.

They are likely to involve methyl tags on DNA, which are used to estimate an organism’s age, the so-called Horvath clock.

One day it might be possible to reprogram cells via pills that stimulate the activity of the OSK factors or the TETs. This may be simpler than it sounds. Natural molecules stimulate the TET enzymes, including vitamin C and alpha-ketoglutarate, a molecule made in mitochondria that is boosted by CR and, when given to nematode worms, extends their lifespan, too.

Tets

In late 2018, a Chinese researcher, He Jiankui, reported that he had helped create the world’s first genetically altered children—twin girls whose births sparked a debate in scientific circles about the ethics of using gene editing to make “designer babies.”

Crispr babies

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.

Targeted sequencing aimed at answering a specific question—such as “What kind of cancer is this?” or “What infection do I have?”—can now be done in less than twenty-four hours. Within ten years, it will be done in a few minutes, and the most expensive part will be the lancet that pricks your finger.3 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. It’s common knowledge that we don’t all respond to drugs in the same way. Sometimes these aren’t small differences in small numbers of people. G6PD genetic deficiency, for instance, affects 300 million people of primarily Asian and African descent. It’s the most common genetic disease of humanity. After ingesting recommended doses of medicines for headaches and malaria and certain antibiotics, G6PD carriers can be caught unawares by hemolysis—what amounts to red blood cell mass suicide.4

I should finally check out dna sequencing given the reduction in price

Treatments that work through insulin or mTOR signaling typically favor females, whereas chemical therapies typically favor males, and no one really knows why.8 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 chromsome 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.

Oh no, not good for me

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.”

Thee Rhonda Patrick herself

your biometric vitals will be the bellwether for your body. If you are a man who has been spending more time in the bathroom than usual, your AI guardian will check for prostate-specific antigens and prostate DNA in your blood, then book you an appointment for a prostate exam. Changes in how you move your hands while speaking, and even the manner in which your strike the keys on your computer,25 will be used to diagnose neurodegenerative diseases years before symptoms would be noticed by you or your doctor. One biotechnological advancement at a time, this world is coming, and fast. Real-time monitoring of our bodies, the likes of which we could hardly have imagined a generation ago, will be as inherent to the experience of living as dashboards are to the experience of driving. And for the first time in history, that will permit us to make data-driven day-to-day health decisions.

periodic visits to the doctor, but they will be almost impossible to miss when our bodies are being measured and monitored all the time. Same, too, for heartbeat irregularities, minor strokes, venous blockages during air medical transport, and many other medical problems that currently are almost always treated in critical care conditions—when it is too late. Before, if you suspected your heart was malfunctioning, and even if you didn’t, it would take a visit to a couple of doctors to get an electrocardiogram. Now millions of people can conduct their own accurate ECG in 30 seconds, wherever they are, just by pressing their finger to the dial on their watch.

flight was in its infancy and most people had never ridden in a car, the H1N1 virus found its way to some of the furthest reaches of our globe. It killed people on remote islands and in arctic villages. It killed without regard to race or national boundaries. It killed like a new Black Death. Average life expectancy in the United States plummeted from 55 to 40 years. It recovered, but not until more than 100 million people of all ages globally had had their lives cut short. This could happen again. And given how much more humans and animals are in contact and how much more interconnected our planet is now than it was a century ago, it could happen quite easily.

David purviewing the old rona

“Whether it occurs by a quirk of nature or at the hand of a terrorist, epidemiologists say a fast-moving airborne pathogen could kill more than 30 million people in less than a year,” Bill Gates told a crowd at the Munich Security Conference in 2017, “and they say there is a reasonable probability the world will experience such an outbreak in the next 10–15 years.”

Ohhh inb4 pandemic

companies, all under one roof. Consolidation has already started and will continue as these companies set their sights on the largest and fastest-growing sector of the global economy, health care, which now exceeds 10 percent of global GNP and is increasing at an annual rate of 4.1 percent.

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. How to get ready for this world is a conversation that needs to be had. And soon. I’m there already. Before I began having my biomarkers checked on a regular basis, I did worry about what the ever-changing chemical signals in my body could disclose about me to someone with access to my data. All the data are held on health care– or HIPAA-compliant servers, and the data are encrypted. But there’s always the fear that the data will be hacked. There’s always a way.

How prescient for David to mention this-- although perhaps the psychological effects of a pandemic are recursive, so he has seen the effects of covid prior to the instantiation. If that's the case, I should probably read up.

But I wasn’t working to solve this problem, until recently. A brush with Lyme disease has a way of intensifying a person’s feelings about these sorts of things.

Our daughter Natalie was 11 years old when it happened. In New England, where we live, there is an epidemic of ticks that carry the bacterial spirochete Borrelia burgdorferi, which causes Lyme disease. Recent estimates suggest that approximately 300,000 people in the United States may contract the disease each year. Left untreated, Borrelia hides out in skin cells and lymph nodes, causing facial paralysis, heart problems, nerve pain, memory loss, and arthritis. It hides in a protective biofilm, making it extremely difficult to kill.

0avril lavigne

The big one is malaria, infecting 219 million people and claiming 435,000 people in 2017.40 Thanks to Bill and Melinda Gates, GlaxoSmithKline, and Program for Appropriate Technology in Health (PATH), a partially effective vaccine against malaria known as Mosquirix was deployed for the first time in 2017, giving hope that the malaria parasite will one day be pushed to extinction.41

Right now, there’s only one way to effectively replace damaged and diseased organs. It’s a morbid truth, but it’s a truth nonetheless: when people pray for an organ to become available for a loved one who needs one, part of what they’re praying for is a deadly car accident. There’s a lot of irony, or some would say logic, in the fact that the Department of Motor Vehicles is the organization that asks people whether they want to be organ donors: each year in the United States alone, more than 35,000 people are killed in motor vehicle accidents, making this mode of death one of the most reliable sources of tissues and organs.

Consider Tom Cruise. As the Top Gun actor entered his late 50s, with bulging muscles and a straight line of dark hair sprouting from a minimally wrinkled forehead, he was still at work. Not just acting, but doing the sort of acting that has long been the purview of much younger actors. He was still doing many of his own dangerous stunts, too: riding motorcycles at high speed through alleys, being strapped to the outside of a plane as it takes off, hanging off the top of the world’s tallest building, skydiving from the upper reaches of the atmosphere. How easily do the words “Fifty is the new thirty” slide from our lips these days? We forget what we used to expect life past 50 to look like, not hundreds of years in the past but just a few decades ago.

David wants to be tom cruise

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.

I'll Have to see a means of getting metformin and the like.

The Road Ahead, Bill Gates made no mention of the internet, though he substantially revised it about a year later, humbly admitting that he had “vastly underestimated how important and how quickly” the internet would come to prominence.

Paul Ehrlich and his wife, associate director of Stanford’s Center for Conservation Biology Anne Ehrlich, sounded the Malthusian alarm once again in a best-selling book called The Population Bomb. When I was young, that book had a rather prominent place on my father’s bookshelf—right at eye level for a young boy. The cover was disturbing: a plump, smiling baby sitting inside a bomb with a lit fuse. I had nightmares about that.

Might give it a read. The haber process is currently sustaining food production, what a twisted irony that haber sustained population growth over the last 100 years.

The problem is not just population, it’s consumption. And it’s not just consumption, it’s waste. In comes the food; out goes the effluent. In come the fossil fuels; out go the carbon emissions. In come the petrochemicals; out goes the plastic. On average, Americans consume more than three times the amount of food they need to survive and about 250 times as much water.14 In return, they produce 4.4 pounds of trash each day, recycling or composting only about of a third of it.

There can also be no debate, at this point, that the melting of the Antarctic and Greenland ice caps is driving a rise in sea levels, which the National Oceanic and Atmospheric Association and others have warned will worsen coastal flooding in the coming years, threatening cities such as New York, Miami, Philadelphia, Houston, Fort Lauderdale, Galveston, Boston, Rio de Janeiro, Amsterdam, Mumbai, Osaka, Guangzhou, and Shanghai. A billion people or more live in areas likely to be affected by rising sea levels.

The quantum physicist Max Planck also knew this to be true. “A new scientific truth does not triumph by convincing its opponents and making them see the light,” Planck wrote shortly before his death in 1947, “but rather because its opponents eventually die, and a new generation grows up that is familiar with it.”26

Harun Onder is among those who have made a demographic observation: nationalist arguments tend to resonate with older people.27 Therefore, it is likely that the antiglobalist wave will be with us for some time to come. “Virtually every country in the world,” the United Nations reported in 2015, “is experiencing growth in the number and proportion of older persons in their population.” Europe and North America already have the largest per capita share of older persons; by 2030, according to the report, those over the age of 60 will account for more than a quarter of the population on both of these continents, and that proportion will continue to grow for decades to come.

We tend to tolerate a bit of bigotry among older people as a condition of the “age in which they grew up,” but perhaps also because we know we won’t have to live with it for long. Consider, though, a world in which people in their 60s will be voting not for another twenty or thirty years but for another sixty or seventy. Imagine a man like Thurmond serving in Congress not for half a century but for an entire century. Or, if it makes it easier to envision from your place on the political spectrum, picture the politician you despise more than any other holding power longer than any other leader in history. Now consider how long despots in far less democratic nations will cling to power—and what they will do with that power.

important insight.

Working with the world-renowned economists Andrew Scott at the University of London and Martin Ellison at Oxford University, we are developing a model to predict what the future looks like. There are quite a few variables, not all of them positive. Will people continue to work? What jobs will they be able to get in a world in which the labor market will already be being upended by automation? Will they spend a half century or more in retirement? Some economists believe that economic growth is slowed when a country ages, in part because people spend less in retirement. What will happen if people spend half of their very long lives out of work, spending only enough to get by?

The choice was clear: adapt or perish.48

Edward O. Wilson, wrote in The Future of Life, “it should be obvious to anyone not in a euphoric delirium that whatever humanity does or does not do, Earth’s capacity to support our species is approaching the limit.”

Hence the dependency on refined carbs

“The idea that humans must live within the natural environmental limits of our planet denies the realities of our entire history, and most likely the future,” he wrote. “… Our planet’s human-carrying capacity emerges from the capabilities of our social systems and our technologies more than from any environmental limits.”53

The current infrastructure that supports our population is not natural so to suggest a natural limit is predicated on scientifically unsound assumptions.

we are naturally compelled to innovate in response.

Bill Gates made a convincing argument for why improving human health is money well spent, and won’t lead to overpopulation, in his 2018 video “Does Saving More Lives Lead to Overpopulation?”56 The short answer is: No.

His tidy equation, which replaced mortality tables, tracks the exponential increase in the chance of death with age. As important as this “law” is to insurance companies, it does not mean that aging is a fact of life.

Economic observation: There has been an influx in adverts I've seen for lif insurance. Given inflation and an extende lifespan I wouldn't see that money until I'm 100. My money would be nowhere near the value that went towards lie insurance. Additionally, the compound interest they'd get on a 100 year old lifespan is nothing short of extraordinary.

Oh, wait. That was 18 percent of people in Australia—which was the most optimistic of the Western nations included in the survey. In the United States, only 6 percent of people were similarly confident that things were getting better in our world. It’s important to note that the pollsters didn’t ask about whether respondents’ individual lives were getting better or worse. They asked about the world. And they asked people in some of the richest nations in the world.57 And sure, these are people who might have reason to think that their individual standards of living—supported until recently by economic benefits rooted in slavery and colonialism—have been falling a bit in recent years. These are also people, however, who have tremendous access to information about the world, and thus, quite frankly, they should know better. In much of the rest of the world, however, the future is not viewed in nearly such a dismal way. Not at all. In China, which holds about a fifth of the global population, some 80 percent of people polled in 2014 by Ipsos MORI, a UK research company, believed the lives of younger people will be better than their own. The same survey identified similarly significant levels of optimism in Brazil, Russia, India, and Turkey—all places where standards of living have been on the rise.58 And yes, this includes habits of increasing consumption, but it also includes lowering birth rates, falling rates of poverty, greater access to clean water and electricity, more ...

Comparison between perceived improvement in western/eastern countries

The Nobel laureate Seamus Heaney described our complicated relationship with aging parents in his poem “The Follower,” ostensibly about his own father, who had shoulders like sails, and Seamus, as a child, “tripping and falling” in his father’s wake. The poem ends, “But today / It is my father who keeps stumbling / Behind me, and will not go away.”

check this poem out

Thanks to the Age Discrimination in Employment Act of 1967, individuals in the United States over age 40 are legally protected from employment discrimination based on age. But in Europe, most workers are forced to retire in their mid-60s, including professors, who are just getting good at what they do. The best ones move to the United States so they can keep on innovating. It’s Europe’s loss, and it’s completely backward.

Asimov made a note of this in his book "i, robot" europe is far too antiquated.

The best way to create jobs for productive people of any age, even less skilled workers, is to build and attract companies that hire highly skilled ones. If you want a country in which your citizens flourish and that others envy, don’t reduce the retirement age or discourage medical treatments for the elderly, hoping to save money and make room for the young. Instead, keep your population healthy and productive, and destroy all barriers to education and innovation.

Dana Goldman had heard from all the naysayers. The University of Southern California economist understood—far more than most people do—that health care costs had risen dramatically over the past decades, not just in his native United States but around the world. He knew those costs were coming at a time in which human lifespans were being extended, resulting in multitudes of patients who were sicker for longer. And he was fully aware of the never-ending nightmare about the future solvency of programs such as Social Security that provide for the common welfare. The prospect of billions of people growing even older seemed like a perfect storm of economic catastrophes. A few years back, however, Goldman began to realize that there was a difference between extending lives and extending healthy lives. As it stands, aging presents a double economic whammy, because adults who get sick stop making money and contributing to society at the same time they start costing a whole lot to keep alive. But what if older people could work longer? What if they were to use fewer health care resources? What if they were able to continue to give back to society through volunteering, mentorship, and other forms of service? Perhaps—just perhaps—the value of those extra healthy years would lessen the economic blow? So Goldman began to crunch the numbers. As any good economist would, he sought to be both rigorous and conservative in his estimation of the benefits of delayed aging.

The psychologists had also recruited forty seminary students to present a talk at the annex. First, though, the students were asked to stop by another building on campus. Once there, some of the seminarians were told they could take their time getting to the annex, others were told they would be on time as long as they left immediately, and a final group was told that they needed to hurry to make it to the annex on time. Just 10 percent of those in the “high-hurry” group stopped to help the man. Those were seminary students, for goodness’ sake, and they ignored a brother in need. One literally stepped over the man in distress to get where he was supposed to be. In the “low-hurry” group, though, more than 60 percent stopped to help. In that experiment, the difference between whether a person made a compassionate choice had nothing to do with personal morality or religious scholarship but whether he felt rushed.

I havebeen vindicated

This isn’t a new idea, of course. Back in the days in which Christ was first telling the Good Samaritan story, his contemporary in ancient Rome Seneca the philosopher was begging his followers to stop and smell the roses. “Life is very short and anxious for those who forget the past, neglect the present, and fear the future,” he wrote.75 For people who don’t appreciate life, time is “reckoned very cheap … in fact without any value,” he lamented. “These people do not know how precious time is.”

medical-industrial complex

One scientist who is particularly annoyed by the budgetary focus on individual diseases is Leonard Hayflick, the scientist who first discovered that human cells in a dish have a limited capacity to divide and eventually senesce, after having reached the Hayflick Limit.

As the Australian example proves, when everyone is living longer and healthier, everyone does better. So why isn’t this a topic of discussion in the United States? Why aren’t people charging Capitol Hill with protest signs and the proverbial pitchforks, demanding more investment, universal access to medicines, and the healthiest lifespan on the planet? As other countries enjoy increasingly longer, healthier lives, perhaps Americans will wake up and smell the disparity. But I suspect they won’t. Though the World Health Organization ranks the United States at number 37, below Dominica, Morocco, and Costa Rica and one up from Slovenia,22 it’s still common to hear US politicians say, without any justification, that the United States has the best health care system in the world, and millions of people believe it.

As the venture capitalist and “very large yacht” owner Nick Hanauer wrote in a memo to “My Fellow Zillionaires” in 2014, “there is no example in human history where wealth accumulated like this and the pitchforks didn’t eventually come out. You show me a highly unequal society, and I will show you a police state. Or an uprising. There are no counterexamples. None. … We will not be able to predict when, and it will be terrible—for everybody. But especially for us.”24

Nearly every day, and often multiple times in a day, someone tells me that they have no interest in living to 100, let alone many decades longer. “If I get to a hundred, just shoot me,” they say. “I think that seventy-five healthy years sounds about right,” they say. “I just can’t imagine having to live with my husband for even longer than I already have to,” one rather distinguished scientist once told me. That’s fine. Indeed, there seems to be little appetite for the idea of living in perpetuity. I recently gave a talk to a general audience of about a hundred people spread across ages 20 to 90, a good cross section of the local community. The main donor to the institute was late, so I had to fill in time. I grabbed the microphone and did a little experiment. “How long do each of you want to live?” I asked. By a show of hands, a third said they’d be happy with 80 years; I told that group that they should all apologize to all the audience members who were older than 80. That got a laugh. Another third indicated that they’d like to see 120. “That’s a good goal,” I said, “and probably not an unrealistic one.” About a quarter wanted to make it to 150. “That’s not a silly thing to dream about anymore,” I said. Only a few people wanted to live “forever.” The numbers were similar at a recent dinner at Harvard for scientists who study aging. Very few of the attendees said they were gunning for immortality. I’ve talked to hundreds of people about this topic. Most people who want i...

CRISPR, for “clustered regularly interspaced short palindromic repeats,” which are the natural DNA targets of Cas9 cutting in bacteria. Cas9, and now dozens of other DNA-editing enzymes from other bacteria, can alter plant genes with accuracy, without using any foreign DNA.

banned. That’s why the decision by the Court of Justice of the European Union in 2018 was so unexpected and upsetting to the United States. The court ruled in favor of Confédération Paysanne, a French agricultural union that defends the interests of small-scale farming, and eight other groups, to ban CRISPR-made foods.40