Lifespan. David Sinclair
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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.105
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.106
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.107
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
The possibility that both genetic and epigenetic aging are needed for a tumor to develop we’ve termed “geroncogenesis,” and it explains why tumors don’t occur in young people even after extreme sun exposure, why it often takes decades for DNA damage to lead to a tumor even if you avoid the sun later in life, and why cancers often have an unusual metabolism (named after the physicist Otto Warburg), one that directly consumes glucose, has decreased mitochondrial activity, and uses less oxygen to make energy, similar to the metabolism of old cells.
According to the World Health Organization, “The State of Global Tobacco Control,” 2008, http://www.who.int/tobacco/mpower/mpower_report_global_control_2008.pdf.
R. A. Miller, “Extending Life: Scientific Prospects and Political Obstacles,”