Lifespan. Dr David A. Sinclair

      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