THREE
THE BLIND EPIDEMIC
IT WAS MAY 10, 2010, and London was abuzz. Chelsea Football Club had just won its fourth national championship by devastating Wigan Athletic, 8–0, on the final day of Premier League play. Meanwhile, Gordon Brown announced that he would be stepping down as prime minister in response to a disastrous parliamentary result for his Labour Party, which had lost more than ninety seats in the previous week’s general election.
With the eyes of the English sports world on one part of London and the attention of the British political universe on another, the goings-on at Carlton House Terrace were missed by all but the most attentive observers of the president, council, and fellows of the Royal Society of London for Improving Natural Knowledge.
More simply known as the Royal Society, the world’s oldest national scientific organization was established in 1660 to promote and disseminate “new science” by big thinkers of the day such as Sir Francis Bacon, the Enlightenment’s promulgator of “the prolongation of life.”1 Befitting its rich scientific history, the society has held annual scientific events ever since. Highlights have included lectures by Sir Isaac Newton on gravity, Charles Babbage on his mechanical computer, and Sir Joseph Banks, who had just arrived back from Australia with a bounty of more than a thousand preserved plants that were all new to science.
Even today, in a post-Enlightenment world, most of the events at the society are fascinating if not world changing. But the two-day meeting that commenced in the spring of 2010 was nothing short of that, for gathered together on that Monday and Tuesday was a motley group of researchers who were meeting to discuss an important “new science.”
The gathering had been called by geneticist Dame Linda Partridge, bioanalytics pioneer Janet Thornton, and molecular neuroscientist Gillian Bates, all luminaries in their respective fields. The attendee list was no less impressive. Cynthia Kenyon spoke about her landmark work on a single mutation in the IGF-1 receptor gene that had doubled the lifespan of roundworms by activating DAF-162—work that was first suggested by Partridge to be a worm-specific aberration3 but soon forced her and other leading researchers to confront long-held beliefs that aging could be controlled by a single gene. Thomas Nyström, from the University of Gothenburg, reported his discovery that Sir2 not only is important for genomic and epigenomic stability in yeast, it also prevents oxidized proteins from being passed on to young daughter cells.
Brian Kennedy, a former Guarente student who was about to assume the presidency of the Buck Institute for Research on Aging, explained the ways in which genetic pathways that had been similarly conserved in a diverse array of species were likely to play similar roles in mammalian aging. Andrzej Bartke from Southern Illinois University, former PhD adviser to Michael “Marathon Mouse” Bonkowski, talked about how dwarf mice can live up to twice as long as normal mice, a record. Molecular biologist María Blasco explained how old mammalian cells are more likely than young cells to lose their identity and become cancerous. And geneticist Nir Barzilai spoke of genetic variants in long-lived humans and his belief that all aging-related diseases can be substantially prevented and human lives can be considerably extended with one relatively easy pharmaceutical intervention.
Over the course of those two days, nineteen presenting scientists from some of the best research institutions in the world moved toward a provocative consensus and began to build a compelling case that would challenge conventional wisdom about human health and disease. Summarizing the meeting for the society later that fall, the biogerontologist David Gems would write that advances in our understanding of organismal senescence are all leading to a momentous singular conclusion: that aging is not an inevitable part of life but rather a “disease process with a broad spectrum of pathological consequences.”4 In this way of thinking, cancer, heart disease, Alzheimer’s, and other conditions we commonly associate with getting old are not necessarily diseases themselves but symptoms of something greater.
Or, put more simply and perhaps even more seditiously: aging itself is a disease.
THE LAW OF HUMAN MORTALITY
If the idea that aging is a disease sounds strange to you, you’re not alone. Physicians and researchers have been avoiding saying that for a long time. Aging, we’ve long been told, is simply the process of growing old. And growing old has long been seen as an inevitable part of life.
We see aging, after all, in nearly everything around us and, in particular, the things around us that look anything like us. The cows and pigs in our farms age. The dogs and cats in our homes do, too. The birds in the sky. The fish in the sea. The trees in the forest. The cells in our petri dishes. It always ends the same way: dust to dust.
The connection between death and aging is so strong that the inevitability of the former governed the way we came to define the latter. When European societies first began keeping public death certificates in the 1600s, aging was a respected cause of death. Descriptions such as “decrepitude” or “feebleness due to old age” were commonly accepted explanations for death. But according to the seventeenth-century English demographer John Graunt, who wrote Natural and Political Observations Mentioned in a Following Index, and Made upon the Bills of Mortality, so were “fright,” “grief,” and “vomiting.”
As we’ve moved forward in time, we’ve moved away from blaming death on old age. No one dies anymore from “getting old.” Over the past century, the Western medical community has come to believe not only that there is always a more immediate cause of death than aging but that it is imperative to identify that cause. In the past few decades, in fact, we’ve become rather fussy about this.
The World Health Organization’s International Classification of Diseases, a list of illnesses, symptoms, and external causes of injury, was launched in 1893 with 161 headings. Today there are more than 14,000, and in most places where records of death are kept, doctors and public health officials use these codes to record both immediate and underlying causes of disability and death.5 That, in turn, helps medical leaders and policy makers around the globe make public health decisions. Broadly speaking, the more often a cause shows up on a death certificate, the more attention society gives to fighting it. This is why heart disease, type 2 diabetes, and dementia are major focuses of research and interventionary medical care, while aging is not, even though aging is the greatest cause of all those diseases.
Age is sometimes considered an underlying factor at the end of someone’s life, but doctors never cite it as an immediate reason for death. Those who do run the risk of raising the ire of bureaucrats, who are prone to send the certificate back to the doctor for further information. Even worse, they are likely to endure the ridicule of their peers. David Gems, the deputy director of the Institute of Healthy Ageing at University College London and the same man who wrote the report from the Royal Society meeting on “the new science of aging,” told Medical Daily in 2015 that “the idea that people die of pure aging, without pathology, is nuts.”6
But this misses the point. Separating aging from disease obfuscates a truth about how we reach the ends of our lives: though it’s certainly important to know why someone fell from a cliff, it’s equally important to know what brought that person to the precipice in the first place.
Aging brings us to the precipice. Give any of us 100 years or so, and it brings us all there.
In 1825, the British actuary Benjamin Gompertz, a learned member of the Royal Society, tried to explain this upward limit with a “Law of Human Mortality,” essentially a mathematical description of aging. He wrote, “It is possible that death may be the consequence of two generally co-existing causes; the one, chance, without previous disposition to death or deterioration; the other, a deterioration, or an increased inability to withstand destruction.”7
The first part of the law says that there is an internal clock that ticks away at random, like the chance a glass at a restaurant will break; essentially a first-order rate reaction, similar to radioactive decay, with some glasses lasting far longer than most. The second part says that, as time passes, due to an unknown runaway process, humans experience an exponential increase in their probability of death. By adding these two components together, Gompertz could accurately predict deaths due to aging: the number of people alive after 50 drops precipitously, but there is a tail at the end where some “lucky” people remain alive beyond what you’d expect. His equations made his relatives, Sir Moses Montefiore and Nathan Mayer Rothschild, owners of the Alliance Insurance Company, a lot of money.
What Gompertz could not have known, but would have appreciated, is that most organisms obey his law: flies, roundworms, mice, even yeast cells. For larger organisms, we don’t know exactly what the two clocks are, but we do know in yeast cells: the chance clock is the formation of an rDNA circle, and the exponential clock is the replication and exponential increase in the numbers of rDNA circles, with the resulting movement of Sir2 away from the silent mating-type genes that causes sterility.8
Humans are more complicated, but in the nineteenth century, British mortality rates were becoming amenable to simple mathematical modeling because they were increasingly avoiding not-from-aging deaths: childbirth, accidents, and infections. This increasingly revealed the underlying and exponential incidence of death due to internal clocks as being the same as it ever was. During those times, the probability of dying doubled every eight years, an equation that left very little room for survivors after the age of 100.
That cap has generally held true ever since, even as the global average life expectancy jumped twenty years between 1960 and today.9 That’s because all that doubling adds up quickly. So even though most people who live in developed nations can now feel confident that they will make it to 80, these days the chances that any of us will reach a century is just 3 in 100. Getting to 115 is a 1-in-100-million proposition. And reaching 130 is a mathematical improbability of the highest order.
At least it is right now.
THE MORTAL BREEZE
Back in the mid-1990s, when I was pursuing my PhD at Australia’s University of New South Wales, my mother, Diana, was found to have a tumor the size of an orange in her left lung.
As she was a lifelong smoker, I’d suspected it was coming. It was the one thing we had argued about more than anything else. When I was a young boy, I used to steal her cigarettes and hide them. It infuriated her. The fact that she didn’t respond to my pleas to stop smoking infuriated me, too.
“I have lived a good life. The rest is a bonus,” she would say to me in her early 40s.
“Do you know how lucky you are to have been born? You’re throwing your life away! I won’t come visit you in hospital when you get cancer,” I would say.
When the cancer finally arrived about a decade later, I wasn’t angry. Tragedy has a way of vanquishing anger. I drove to the hospital, determined to solve any problem.
My mother was responsible for her own actions, but she was also a victim of an unscrupulous industry. Tobacco alone doesn’t kill people; it’s the combination of tobacco, genetics, and time that most often leads to death. She was diagnosed with cancer at the age of 50. That’s twenty-one years earlier than the first diagnosis in the average lung cancer patient. It’s also how old I am now.
In one way of thinking, my mother was unfortunate to develop cancer at such a young age. After her back was opened up, rows of ribs were cut from her spine, and major arteries were rerouted, she lived the rest of her life with just one lung, which certainly impacted her quality of life and ensured that she had only a few years of good life left.
On the genetics front, my mother was also unfortunate. Everyone in my family, from my grandmother to my youngest son, has had their genes analyzed by one of the companies that offer these services. When my mother had hers done, she learned, albeit after she had cancer, that she had inherited a mutation in the SERPINA1 gene, which is implicated in chronic obstructive pulmonary disease or emphysema. That meant her clock was ticking even faster. After her left lung was removed, her right lung was the sole provider of oxygen, but the deficiency in SERPINA1 meant that white blood cells attacked her remaining lung, destroying the tissue as if it were an invader. Eventually the lung gave out.10
In another way of thinking, though, my mother was very lucky—she had the come-to-God moment that many smokers need to go to battle with the tremendously powerful forces of addiction in time to save herself, and she spent another two decades on this planet. She traveled the world, visiting eighteen different countries. She met her grandchildren. She saw me give a TED Talk at the Sydney Opera House. For this we must certainly credit the doctors who removed her cancerous lung, but we should also acknowledge the positive impact of her age. One of the best ways to predict whether someone will survive a disease, after all, is to take a look at how old he or she is when diagnosed—and my mother was, relatively speaking, very young.
This is key. We know that smoking accelerates the aging clock and makes you more likely to die than a nonsmoker—15 years earlier, on average. So, we have fought it with public health campaigns, class action lawsuits, taxes on tobacco products, and legislation. We know that cancer makes you more likely to die, and we’ve fought it with billions of dollars’ worth of research aimed at ending it once and for all.
We know that aging makes you more likely to die, too, but we’ve accepted it as part of life.
It’s also worth noting that even before my mother was diagnosed with lung cancer—indeed, even before the cancerous cells in her lungs began growing out of control—she was aging. And in that way, of course, she was hardly unique. We know that the process of aging begins long before we notice it. And with the unfortunate exceptions of those whose lives are taken by the early onset of a hereditary ailment or a deadly pathogen, most people begin to experience at least some of the effects of aging long before they are impacted by the accumulation of diseases we commonly associate with growing old. At the molecular level, this starts to happen at a time in our lives that many of us still look and feel young. Girls who go through puberty earlier than normal, for example, have an accelerated epigenetic clock. At that age, we can’t hear the mistakes of the concert pianist.11 But they are there, even as a teenager.
In our 40s and 50s, we don’t often think about what it feels like to grow old. When I give talks about my research, sometimes I bring an “age suit” and ask a young volunteer to wear it. A neck brace reduces mobility in the neck, lead-lined jackets and wraps all over the body simulate weak muscles, earplugs reduce hearing, and ski goggles simulate cataracts. After a few minutes of walking around in the suit, the test subject is very relieved to take it off—and fortunately can do so.
“Imagine wearing it for a decade,” I say.
To put yourself into an aged mind-set, try this little experiment. Using your nondominant hand, write your name, address, and phone number while circling your opposite foot counterclockwise. That’s a rough approximation of what it feels like.
Different functions peak at different times for different people, but physical fitness, in general, begins to decline in our 20s and 30s. Men who run middle-distance races, for instance, are fastest around the age of 25, no matter how hard they train after that. The best female marathoners can stay competitive well into their late 20s and early 30s, but their times begin to rise quickly after 40. Occasionally, exceptionally fit outliers—such as National Football League quarterback Tom Brady, National Women’s Soccer League defender Christie Pearce, Major League Baseball outfielder Ichiro Suzuki, and tennis legend Martina Navratilova—demonstrate that professional athletes can stay competitive into their 40s, but almost no one remains at the highest levels of these or most other professional sports much past their mid-40s. Even someone as resilient as Navratilova peaked when she was in her early 20s through her early 30s.
There are some simple tests to determine how biologically old you probably are. The number of push-ups you can do is a good indicator. If you are over 45 and can do more than twenty, you are doing well. The other test of age is the sitting-rising test (SRT). Sit on the floor, barefooted, with legs crossed. Lean forward quickly and see if you can get up in one move. A young person can. A middle-aged person typically needs to push off with one of their hands. An elderly person often needs to get onto one knee. A study of people 51 to 80 years found that 157 out of 159 people who passed away in 75 months had received less than perfect SRT scores.
Physical changes happen to everyone. Our skin wrinkles. Our hair grays. Our joints ache. We start groaning when we get up. We begin to lose resilience, not just to diseases but to all of life’s bumps and bruises.
Fortunately, a hip fracture for a teenager is a very rare event that nearly everyone is expected to bounce back from. At 50, such an injury could be a life-altering event but generally not a fatal one. It’s not long after that, though, that the risk factor for people who suffer a broken hip becomes terrifyingly high. Some reports show that up to half of those over the age of 65 who suffer a hip fracture will die within six months.12 And those who survive often live the rest of their lives in pain and with limited mobility. At 88, my grandmother Vera tripped on a rumpled carpet and broke her upper femur. During surgery to repair the damage, her heart stopped on the operating table. Though she survived, her brain had been starved for oxygen. She never walked again and died a few years later.
Wounds also heal much more slowly with age—a phenomenon first scientifically studied during World War I by the French biophysicist Pierre Lecomte du Noüy, who noted a difference in the rate of healing between younger and older wounded soldiers. We can see this in even starker relief when we look at the differences in the ways children and the elderly heal from wounds. When a child gets a cut on her foot, a noninfected wound will heal quite quickly. The only medicine most kids need when they get hurt like this is a kiss, a Band-Aid, and some assurance that everything will be okay. For an elderly person, a foot injury is not just painful but dangerous. For older diabetics, in particular, a small wound can be deadly: The five-year mortality rate for a foot ulcer in a diabetic is greater than 50 percent. That’s higher than the death rates for many kinds of cancer.13
Chronic foot wounds, by the way, are not rare; we just don’t hear much about them. They almost always begin with seemingly benign rubbing on increasingly numb and fragile soles—but not always. My friend David Armstrong, at the University of Southern California, a passionate advocate for increasing our focus on preventing diabetic foot injuries, often tells the story of one of his patients, who had a nail stuck in his foot for four days. The patient noticed it only because he wondered where the tapping sound on the floor was coming from.
Small and large diabetic foot wounds rarely heal. They can look as though someone has taken an apple corer to the balls of both feet. The body doesn’t have enough blood flow and cell regeneration capacity, and bacteria thrive in this meaty, moist environment. Right now, 40 million people, bedridden and waiting for death, are living this nightmare. There’s almost nothing that can be done for them except to cut back the dead and dying tissue, then cut some more, and then some more. From there, robbed of upright mobility, misery is your bedfellow and thankfully death is nigh. In the United States alone, each year, 82,000 elderly people have a limb amputated. That’s ten every hour. All this pain, all this cost, comes from relatively minor initial injuries: foot wounds.
The older we get, the less it takes for an injury or illness to drive us to our deaths. We are pushed closer and closer to the precipice until it takes nothing more than a gentle wind to send us over. This is the very definition of frailty.
If hepatitis, kidney disease, or melanoma did the sorts of things to us that aging does, we would put those diseases on a list of the deadliest illnesses in the world. Instead, scientists call what happens to us a “loss of resilience,” and we generally have accepted it as part of the human condition.
There is nothing more dangerous to us than age. Yet we have conceded its power over us. And we have turned our fight for better health in other directions.
WHACK-A-MOLE MEDICINE
There are three large hospitals within a few minutes walk of my office. Brigham and Women’s Hospital, Beth Israel Deaconess Medical Center, and Boston Children’s Hospital are focused on different patient populations and medical specialties, but they’re all set up the same way.
If we were to take a walk into the lobby of Brigham and Women’s and head over to the sign by the elevator, we’d get a lay of this nearly universal medical landscape. On the first floor is wound care. Second floor: orthopedics. Third floor: gynecology and obstetrics. Fourth floor: pulmonary care.
At Boston Children’s, the different medical specialties are similarly separated, though they are labeled in a way more befitting the young patients at this amazing hospital. Follow the signs with the boats for psychiatry. The flowers will take you to the cystic fibrosis center. The fish will get you to immunology.
And now over to Beth Israel. This way to the cancer center. That way to dermatology. Over here for infectious diseases.
The research centers that surround these three hospitals are set up in much the same way. In one lab you’ll find researchers working to cure cancer. In another they’re fighting diabetes. In yet another they’re working on heart disease. Sure, there are geriatricians, but they almost always take care of the already sick, thirty years too late. They treat the aged—not the aging. No wonder so few doctors today are choosing to specialize in this area of medicine.
There’s a reason why hospitals and research institutions are organized in this way. Most of our modern medical culture has been built to address medical problems one by one—a segregation that owes itself in no small part to our obsession with classifying the specific pathologies leading to death.
There was nothing wrong with this setup when it was established hundreds of years ago. And by and large, it still works today. But what this approach ignores is that stopping the progression of one disease doesn’t make it any less likely that a person will die of another. Sometimes, in fact, the treatment for one disease can be an aggravating factor for another. Chemotherapy can cure some forms of cancer, for instance, but it also makes people’s bodies more susceptible to other forms of cancer. And as we learned in the case of my grandmother Vera, something as seemingly routine as orthopedic surgery can make patients more susceptible to heart failure.
Because the stakes are so exceptionally high for the individual patients being treated in these places, a lot of people don’t recognize that a battle won on any of these individual fronts won’t make much of a difference against the Law of Human Mortality. Surviving cancer or heart disease doesn’t substantially increase the average human lifespan, it just decreases the odds of dying of cancer or heart disease.
The way doctors treat illness today “is simple,” wrote S. Jay Olshansky, a demographer at the University of Illinois. “As soon as a disease appears, attack that disease as if nothing else is present; beat the disease down, and once you succeed, push the patient out the door until he or she faces the next challenge; then beat that one down. Repeat until failure.”14
The United States spends hundreds of billions of dollars each year fighting cardiovascular disease.15 But if we could stop all cardiovascular disease—every single case, all at once—we wouldn’t add many years to the average lifespan; the gain would be just 1.5 years. The same is true for cancer; stopping all forms of that scourge would give us just 2.1 more years of life on average, because all other causes of death still increase exponentially. We’re still aging, after all.
Aging in its final stages is nothing like a bushwalk, where a bit of rest, a drink of water, a nutritional bar, and some fresh socks can get you another dozen miles before sunset. It’s more like a fast sprint over an ever-higher and ever-closer set of hurdles. One of those hurdles will eventually send you for a tumble. And once you’ve fallen one time, if you do get up, the odds of falling again just keep getting higher. Take away one hurdle, and the path forward is really no less precarious. That’s why the current solutions, which are focused on curing individual diseases, are both very expensive and very ineffective when it comes to making big advances in prolonging our healthspans. What we need are medicines that knock down all the hurdles.
WHY TREATING ONE DISEASE AT A TIME HAS LITTLE IMPACT ON LIFESPAN. The graph shows an exponential increase in disease as each year passes after the age of 20. It’s hard to appreciate exponential graphs. If I were to draw this graph with a linear Y-axis, it would be two stories tall. What this means is your chance of developing a lethal disease increases by a thousandfold between the ages of 20 and 70, so preventing one disease makes little difference to lifespan.
Source: Adapted from A. Zenin, Y. Tsepilov, S. Sharapov, et al., “Identification of 12 Genetic Loci Associated with Human Healthspan,” Communications Biology 2 (January 2019).
Thanks to statins, triple-bypass surgeries, defibrillators, transplants, and other medical interventions, our hearts are staying alive longer than ever. But we haven’t been nearly so attentive to our other organs, including the most important one of all: our brains. The result is that more of us are spending more years suffering from brain-related maladies, such as dementia.
Eileen Crimmins, who studies health, mortality, and global aging at the University of Southern California, has observed that even though average lifespans in the United States have increased in recent decades, our healthspans have not kept up. “We have reduced mortality more than we prevented morbidity,” she wrote in 2015.16
So prevalent is the combined problem of early mortality and morbidity that there is a statistic for it: the disability-adjusted life year, or DALY, which measures the years of life lost from both premature death and poor state of health. The Russian DALY is the highest in Europe, with twenty-five lost years of healthy life per person. In Israel, it is an impressive ten years. In the United States, the number is a dismal twenty-three.17
The average age of death can vary rather significantly over time, and is affected by many factors, including the prevalence of obesity, sedentary lifestyles, and drug overdoses. Similarly, the very idea of poor health is both subjective and measured differently from place to place, and so researchers are divided on whether the DALY is rising or declining in the United States. But even the more optimistic assessments suggest that the numbers have largely been static in recent years. To me, that in itself is an indictment of the US system; like other advanced countries, we should be making tremendous progress toward reducing the DALY and other measures of morbidity, yet, at best, it seems we’re treading water. We need a new approach.
It doesn’t take studies and statistics to know what’s happening, though. It’s all around us, and the older we get, the more obvious it becomes. We get to 50 and begin to notice we look like our parents, with graying hair and an increasing number of wrinkles. We get to 65, and if we haven’t faced some form of disease or disability yet, we consider ourselves fortunate. If we’re still around at 80, we are almost guaranteed to be combating an ailment that has made life harder, less comfortable, and less joyful. One study found that 85-year-old men are diagnosed with an average of four different diseases, with women of that age suffering from five. Heart disease and cancer. Arthritis and Alzheimer’s. Kidney disease and diabetes. Most patients have several additional undiagnosed diseases, including hypertension, ischemic heart disease, atrial fibrillation, and dementia.18 Yes, these are different ailments with different pathologies, studied in different buildings at the National Institutes of Health and in different departments within universities.
But aging is a risk factor for all of them.
In fact, it’s the risk factor. Truly, by comparison, little else matters.
The final years of my mother’s life serve as a good example. Like almost everyone else, I recognized that smoking would increase my mother’s chances of getting lung cancer. I also knew why: cigarette smoke contains a chemical called benzo(a)pyrene, which binds to guanine in DNA, induces double-strand breaks, and causes mutations. The repair process also causes epigenetic drift and metabolic changes that cancer cells thrive on, in a process we’ve called geroncogenesis.19
The combination of genetic and epigenetic changes induced by years of exposure to cigarette smoke increases the chances of developing lung cancer about fivefold.
That’s a big increase. And because of it—and the devastatingly high health costs associated with treating cancer—the majority of the world’s nations sponsor smoking cessation programs. Most countries also put health warnings on cigarette packaging, some with horrific color pictures of tumors and blackened extremities. Most countries have passed laws against certain kinds of tobacco advertising. And most have sought to decrease consumption through punitive taxes.20
All of that to prevent a fivefold increase in a few kinds of cancer. And having watched my mother suffer from that kind of cancer, I’ll be the first to say it’s totally worth it. From both an economic and emotional point of view, these are good investments.
But consider this: though smoking increases the risk of getting cancer fivefold, being 50 years old increases your cancer risk a hundredfold. By the age of 70, it is a thousandfold.21
Such exponentially increasing odds also apply to heart disease. And diabetes. And dementia. The list goes on and on. Yet there is not a country in the world that has committed any significant resources to help its citizens combat aging. In a world in which we seem to agree on very little, the feeling that “it’s just the way it goes” is almost universal.
A GLORIOUS FIGHT
Aging results in physical decline.
It limits the quality of life.
And it has a specific pathology.
Aging does all this, and in doing so it fulfills every category of what we call a disease except one: it impacts more than half the population.
According to The Merck Manual of Geriatrics, a malady that impacts less than half the population is a disease. But aging, of course, impacts everyone. The manual therefore calls aging an “inevitable, irreversible decline in organ function that occurs over time even in the absence of injury, illness, environmental risks, or poor lifestyle choices.”
Can you imagine saying that cancer is inevitable and irreversible? Or diabetes? Or gangrene?
I can. Because we used to say that.
All of these may be natural problems, but that doesn’t make them inevitable and irreversible—and it sure doesn’t make them acceptable. The manual is wrong about aging.
But being wrong has never stopped conventional wisdom from negatively impacting public policy. And because aging isn’t a disease by the commonly accepted definition, it doesn’t fit nicely into the system we’ve built for funding medical research, drug development, and the reimbursement of medical costs by insurance companies. Words matter. Definitions matter. Framing matters. And the words, definitions, and framing we use to describe aging are all about inevitability. We didn’t just throw in the towel before the fight began, we threw it in before we even knew there was a fight to be had.
But there is a fight. A glorious and global one. And, I think, a winnable one.
There’s no good reason why we have to say that something that happens to 49.9 percent of the population is a disease while something that happens to 50.1 percent of the population is not. In fact, that’s a backward way of approaching problems that lends itself to the whack-a-mole system of medicine we’ve set up in hospitals and research centers around the world.
Why would we choose to focus on problems that impact small groups of people if we could address the problem that impacts everyone—especially if, in doing so, we could significantly impact all those other, smaller problems?
We can.
I believe that aging is a disease. I believe it is treatable. I believe we can treat it within our lifetimes. And in doing so, I believe, everything we know about human health will be fundamentally changed.
If you are not yet convinced that aging is a disease, I want to let you in on a secret. I have a window into the future. In 2028, a scientist will discover a new virus, called LINE-1. It will turn out that we are all infected with it. We get it from our parents. It will turn out that the LINE-1 virus is responsible for most other major diseases: diabetes, heart disease, cancer, dementia. It causes a slow, horrible chronic disorder, and all humans eventually succumb to it, even if they have a low-grade infection. Fortunately, the world pours billions of dollars into finding a cure. In 2033, a company will succeed in making a vaccine that prevents LINE-1 infections. New generations who are vaccinated at birth will live fifty years longer than their parents did—it will turn out that that’s our natural lifespan and we had no idea. The new generation of healthy humans will pity previous generations, who blindly accepted that physical decline at 50 was natural and an 80-year life was a life well lived.
Of course, this is a science fiction story I just invented. But it might be truer than you think.
A few recent studies have suggested that the so-called selfish genes we all carry in our genome, actually called LINE-1 elements, replicate and cause cellular havoc as we get older, accelerating our physical demise. We’ll discuss them in more detail later, but for now, it’s the idea I want to focus on because it raises important questions: Does it matter whether LINE-1 comes from your parents directly or via a virus? Would you want to eradicate LINE-1 from humanity or let it grow in your kids and inflict horrible diseases on them? Would you say that LINE-1 causes a disease or not?
If not, is it simply because more than half of all people carry it?
Whether it’s a virus, a selfish DNA element, or simply the makeup of our cells that causes these health problems, what’s the difference? The end result is the same.
The belief that aging is a natural process is deep-rooted. So even if I’ve somewhat convinced you that aging should be considered a disease, let’s do another thought experiment.
Imagine that everyone on our planet typically lives to 150 years in good health. Your family, though, doesn’t. You become wrinkled, gray-haired, diabetic, and frail at 80. Upon seeing these poor, unfortunate souls in this poor, unfortunate state of existence, what doctor would not diagnose your family with a disease, name it after him- or herself, and publish horrid photos of you with your eyes blacked out in medical journals? Communities would raise money to understand and find a cure for your family’s wretched inheritance.
That was exactly what happened when the German physician Otto Werner first described a condition that causes people to look and feel as though they are 80 when they are in their 40s. That’s Werner syndrome, the disease I was studying when I first arrived at MIT in the 1990s. Nobody said I was studying something that is inevitable or irreversible. Nobody said it was crazy to call Werner syndrome a disease or to work to find a breakthrough therapy. Nobody told me or the Werner patients that “that’s just the way it goes.”
In front of us is the deadliest and costliest disease on the planet, a disease that almost no one is working on. It is as if the planet is in a stupor. If your first thought is “But I don’t want to live past 90,” let me assure you: I don’t want you to live a year longer than you wish.
But before you make your decision, let’s do one final thought experiment.
Imagine that a clerk at City Hall has found a mistake on your birth certificate. It turns out that you are actually 92 years old.
“You’ll get a new one in the mail,” the clerk says. “Have a nice day.”
Do you feel any different now that you are 92? Nothing else has changed in your life—just a few numbers on your identification. Do you suddenly want to kill yourself?
Of course not. When we stay healthy and vibrant, as long as we feel young physically and mentally, our age doesn’t matter. That’s true whether you are 32, 52, or 92. Most middle-aged and older adults in the United States report feeling ten to twenty years younger than their age, because they still feel healthy. And feeling younger than your age predicts lower mortality and better cognitive abilities later in life.22 It’s a virtuous cycle, as long as you keep pedaling.
But no matter how you feel at this moment in your life, even with a positive outlook and a healthy lifestyle, you have a disease. And it’s going to catch up to you, sooner rather than later, unless something is done.
I acknowledge that calling aging a disease is a radical departure from the mainstream view of health and well-being, which has established an array of medical interventions addressing the various causes of death. That framework evolved, however, largely because we didn’t understand why aging occurs. Up until very recently, the best thing we had was a list of aging hallmarks. The Information Theory of Aging could change that.
There is nothing wrong with using the hallmarks to guide interventions. We can probably have a positive impact on people’s lives by addressing each of them. It’s possible that interventions aimed at slowing telomere deterioration will improve people’s long-term well-being. Maintaining proteostasis, preventing deregulation of nutrient sensing, thwarting mitochondrial dysfunction, stopping senescence, rejuvenating stem cells, and decreasing inflammation might all be ways to delay the inevitable. Indeed, I work with students, postdocs, and companies around the globe that are developing solutions to each one of these hallmarks and hope to continue.23 Anything we can do to alleviate suffering we should do.
But we’re still building nine dams on nine tributaries.
In coming together to tackle the “new science of aging,” as the attendees of the Royal Society meeting termed this fight in their 2010 meeting, increasing numbers of scientists are starting to acknowledge the possibility and potential inherent in heading upstream.
Together we can build a single dam—at the source. Not just intervene when things go wrong. Not just slow things down. We can eliminate the symptoms of aging altogether.
This disease is treatable.