It was a warm summer day in 1968, and a breeze rippled the leaves on the trees that lined Panorama Street as my grandfather Dov and I walked to the top of Mount Carmel, where we could see Haifa Bay. Across the bay were the Galilee mountains, Nazareth, and Golan Heights. I was thirteen and Grandfather was sixty-eight, and we walked this route nearly every Saturday as he told me stories about his life. My sisters and I were born in Haifa and grew up there, as did our father, so many of the stories’ settings were familiar to me. On this day, he told me the story of planting trees on the roads to Jerusalem and draining swamps in Hadera. I idolized him and hung on his every word as he explained the challenges involved and the strength required to accomplish those tasks.
Each of his stories made him seem larger than life—strong, active, unwavering. But as we crested the hill, he was breathing heavily and leaned over, placing his hands on his thighs as if he might topple over. I stood watching him, wondering if there was something I should do to help him. I’d never seen him so out of breath. How could this slow, overweight man—balding and wrinkled—be the man from the stories? How could he plant trees and drain swamps and build businesses? How could that person have become this person?
Grandfather continued his story a minute later, but that moment sparked the first of the great mysteries in my life, one that ultimately helped push me into medicine and has tantalized me for decades. Aging transforms us, remakes us, breaks us, destroys us. But why?
I’m still asking that question, and as I near the age my grandfather was on that memorable day, my quest has taken on new meaning. My grandfather died of a heart attack at age sixty-eight, but thanks to improvements that have been made in medical interventions over the past hundred years, my father, David, who had a heart attack at the same age, underwent triple bypass surgery and lived another two decades. And preventive measures have improved so much that I’m planning to skip the heart attack altogether.
For thousands of years before the twentieth century, most people died between the ages of twenty-five and thirty-five. Forty years old was considered ancient. Of course, there were always exceptions, and we know that some people, like Leonardo da Vinci and Rembrandt, lived to be very old, but it wasn’t until the twentieth century that life expectancy for men and women exceeded sixty years, thanks to sanitation, immunizations, antibiotics, medication, surgery, and other innovations. By the mid-1900s, human life span increased until the average reached eighty years, which is where we are now. But we start accumulating diseases after the age of sixty, and many people are being treated for three different diseases or chronic conditions by the age of seventy-five. So regarding the future of humanity and quality of life, it’s clear that finding a way to prevent or delay the onset of age-related illnesses is one of the most important mysteries we can solve. I have dedicated my life to this quest, not just because of the vision I have for the future but also because of some lessons from my past.
When I was a medical student at the Israeli Institute of Technology, I was also a medic and a nurse, so I wanted to use my knowledge and skills to help wherever they were needed most. My first opportunity was during the winter of 1979/80 when Vietnam invaded Cambodia and overthrew the oppressive regime of Pol Pot and his “killing fields.” I was one of ten people on the Israeli government mission team that traveled to the border of Cambodia and Thailand to work in the Sakeo refugee camp under the auspices of the Red Cross. These refugees, many of whom had been soldiers under Pol Pot’s rule, were dying of the same things that have afflicted humankind since the beginning of our existence—namely, infectious disease, starvation, and violent conflict with other humans. We saved thousands of lives, but for each one we saved, another dozen died. Despite this nightmare, all the volunteers worked relentlessly, including the Salvation Army missionaries, who had set up a small shelter in the middle of camp where children could have a drink and a snack while the volunteers told them Bible stories. So everyone was offering whatever skills and services we could provide, and eventually, we made some progress by keeping more of the refugees alive.
But we also saw many people die before they had a chance to grow old, and that had a lasting impact on me and gave me a deeper appreciation for life. It also made me think of how fortunate my grandfather had been to live so long even though his last years were not healthy. And the question was sparked again: Why can’t we live long and be healthy?
My time working in the Cambodian refugee camp also taught me something that empowered me to keep searching for the answer to that question. This unexpected lesson came to me by way of three Buddhist monks who approached me one day as I was in the storage shed, looking for supplies. They greeted me with their hands clasped in prayer, two middle-aged men wearing yellow gowns and an older man wearing orange. He spoke fluent English but surprised me by saying, “Shalom,” and other Hebrew words. He said he was the Tana-Jan, the high Buddhist priest for large areas of Cambodia, Thailand, and Laos, and he invited me and other members of the Israeli team to his temple to discuss a problem of grave importance.
That night, four of us and a guide traveled what felt like a very long way to the temple. But when the guide stopped the van, all we could see was a narrow path that led into the jungle. He instructed us to stay close behind him, and we walked through the dense foliage in the dimming light. The sounds that the birds and other animals in the jungle were making were unfamiliar and intimidating, but our guide pressed on until we finally reached a clearing and a small, one-story temple made of wood.
The Tana-Jan welcomed us and invited us inside. The room was huge and mostly empty, but on the bookshelves were many foreign-language dictionaries, books written in Latin, and books on Islam and Christianity. I was surprised to see that there were also Hebrew books and books about Judaism. He invited us to meditate with him, and while we were unable to reach his level of tranquility, as physicians, we were most impressed by his unnaturally low pulse rate (which we could measure by looking at the pulsation of the carotid artery in his neck). After meditation, the Tana-Jan explained that he had decided to speak to “the chosen people” about his distress. I had thought he had a medical question, but that was not the case. He explained that he was concerned that the missionary action of the Salvation Army would lead Buddhist children in the camp to convert to Christianity for the small gift of drink and food. He felt that these distressed youths were not able to make decisions based on free choice. He thought that as Jews, we could negotiate between the Christians and the Buddhists and stop what he perceived to be a disaster.
I was surprised and overwhelmed by his request. All of a sudden, I questioned whether Major Eva’s well-intentioned efforts were appropriate. But at the same time, I’d witnessed how comforting religious beliefs were to those who were sick and had lost loved ones or were facing death themselves. So I thought that if there were a place in the camp for the refugees to practice their own religion, that could promote their well-being.
We returned to the camp the next morning and negotiated a deal with the Red Cross administrator of the camp. Next to the Salvation Army shed, a shed for the Buddhist followers was to be erected. Children would still get food and drink, but they could choose which shed to go to. As it worked out, after that second shed was built, we saw children and other refugees in both places. Coming from the Middle East, where religious conflict has been a cause of wars and misery, I felt that facilitating peace between two religious groups was one of the most significant contributions we could make to the refugees because peace allows for healing, reparation, and life.
Solving the conflict between the Christians and the Buddhists at the refugee camp is one of the experiences that taught me that I could set goals that some may think are unattainable and achieve great things with help from others and a little bit of luck. Without this knowledge, I may not have thought to take on the uphill battle to prove that the hallmarks of aging can be targeted to delay aging and its diseases. While I was full of hope when I began my journey into the biology of aging, very few people shared my enthusiasm, and many people thought that my goal was unachievable. Early studies provided clues that were encouraging, though, and within a decade, the new field of geroscience was thriving, and my colleagues and I have shown through a variety of research studies that aging can, in fact, be targeted. Today, we’re focused on making this knowledge applicable for the general public by exploring and developing new treatments and drugs that target the causes of aging.
My journey parallels the evolution of this discovery. Along the way, I’ve studied animal models and discovered mechanisms for exceptional longevity in humans. To shorten the time line between research and human application, I have also taken on a leadership role in solving the challenges involved with proving that targeting aging can prevent an array of age-related diseases.
In a very short period of time, geroscientists have revolutionized the discipline: to think of aging not as a certainty but as a phenomenon—like many other difficult conditions—that can be targeted, improved, and even cured as if it were a disease. To that end, we are creating biotech companies and other ventures so that as soon as our nationwide double-blind human clinical trial produces the evidence needed by the FDA, more treatments, new drugs, and combinations of drugs that slow aging and increase health span will become available.
After decades of direct research as well as nationwide and worldwide collaborative projects that brought previously isolated researchers together, we are finally able to say that aging, as we know it, is over.
ONE HUNDRED YEARS YOUNG
Have you heard the one about the woman who asked her eighty-year-old husband, “Want to go upstairs and make love?”
“I’m sorry, honey,” he said. “I can’t do both.”
In the near future, the punch line may not work. Having overcome these limitations, we will be enjoying a new reality of being healthy and vital in our nineties and beyond. We are on the leading edge of a revolution that will dramatically change the way we age. It may sound like science fiction, but I promise you it’s science. To be exact, it’s geroscience, an interdisciplinary field that studies the relationship between aging and age-related diseases. This collaboration has built a bridge between the interests of biologists exploring the basic mechanisms that drive aging and geriatricians trying to improve elderly patients’ quality of life. And I’m delighted to report that the future is very bright.
This new reality is made possible by what we’re learning from centenarians like the Kahn siblings—Irving, Helen, Peter, and Leonore. The four children had been born during the first decade of the twentieth century, when the average life expectancy at birth was only forty years. They’d seen each other through wars, deaths, and divorces and celebrated together at the birth of grandchildren and great-grandchildren. Leonore and Helen had joined the first Girl Scout troop in New York, and as an adult, Leonore became a troop leader and trained volunteers for more than fifty years. Helen enjoyed a long career as a magazine writer, which she began in 1936. Peter was a cameraman on such movies as Gone with the Wind and The Wizard of Oz and a photographer with Frank Capra in the Pacific theater of World War II. He also helped to develop Technicolor and worked in video technology at HBO until retiring at eighty-one. Irving first went to work on Wall Street in 1928, before the Great Depression. Everything imaginable had changed over the course of their lives, but in a physical sense, time seemed to be standing still for these four siblings.
Yes, they’d aged. But the changes we associate with aging—lost mobility, lost intellect, lost excitement, lost energy—had been delayed for decades. They lived more than two and a half times as long as most of their peers, and instead of declining, they each continued to thrive. Leonore was still giving tours at an environmental learning center well into her nineties. Irving continued to work at the family investment firm at 108, bossing around his son and grandson who also worked there. Peter remarried at seventy-three and was happy with his new wife for more than thirty years. Helen drank Budweiser, went to Manhattan museums and trendy restaurants, and smoked for more than ninety years.
That’s what makes the Kahns so extraordinary. They weren’t eating anything special, exercising outside their daily routines, drinking extra water, napping, or doing anything else that we tend to think of as healthy, life-extending habits. They didn’t strive to keep their bodies whole and their minds nimble—they just, somehow, were.
Like many centenarians, the Kahns simply aged more slowly than most of the population—meaning they, in effect, aged later. But why? That’s the question I’ve been studying for almost two decades, and I have encouraging news. Scientific advances are making the sandwich generation a thing of the past. Instead of being pulled in two directions by needing to care for our aging parents while we raise our children, we can watch our healthy parents play active roles in their grandchildren’s lives.
* * *
Later in the book, you’ll learn more about Irving Kahn, along with some of our other centenarians, including:
Ervin Adam, ninety-seven, my uncle and one of the most resilient people I have ever known. After surviving six concentration camps during World War II and fleeing Czechoslovakia as the Soviets invaded in 1968, he bounced back again after losing everything to Hurricane Harvey in 2017. And after finally retiring from the Baylor College of Medicine at ninety-four, he still attends lectures every week.My wife’s grandmother Frieda, another centenarian who defied the medical texts. Remarkably active and determined to keep enjoying life, she broke her ankle at age one hundred, and she insisted on having surgery even though her doctor thought a wheelchair would be a safer option.And this new frontier isn’t just exciting from the standpoint of slowing aging and the onset of disease—it also has other profound implications. People who undergo chemotherapy or radiation treatment age rapidly, and that places them at higher risk for another disease or a second cancer. And the children who survive after having these treatments start having age-related diseases, such as hypertension and cardiovascular disease, at much younger ages than we see in the general population. These people desperately need our help, as do people with HIV. The treatment they receive to survive may be aging them faster than the virus, and on average, they get all the age-related diseases about ten years sooner than people who do not have HIV. Another large group of people who need interventions against rapid aging are those with physical disabilities and permanent injuries who cannot exercise as much as others can and tend to become obese, which accelerates aging. All these people can benefit from the new treatments and drugs that are being developed, so targeting the causes of aging truly benefits many more groups than the elderly. And the benefits of these new developments even extend beyond our sick and suffering. They will be vitally important in our quest to reach new frontiers, on the planet and off. When astronauts make the voyage to Mars, they will be exposed to radiation for years, and the discoveries we make with genetic testing and research will also lead to revolutionary approaches to protecting people when they leave Earth’s atmosphere.
The Mysteries of Aging
We can understand why the circle of life includes death, but aging is different. Why would an organism evolve to deteriorate as it grows older? How does it benefit us as a species to have eyesight dwindle, mobility decline, stamina evaporate, bones wither, and bellies get bigger? As a scientist and a gerontologist, I assure you that these losses and indignities no longer need to define the last decades of our lives. When we ask people in the United States how long they want to live, they usually say between seventy-nine and a hundred years, and in one study, the median number of years was ninety, but those responses are influenced by the effects of old age that people have witnessed, and the past does not dictate the future. An average U.S. life span of eighty-nine is just the current norm. When people can live beyond one hundred while maintaining their faculties and enjoying good health, we might feel shortchanged if we only make it to ninety-five.
Growing old may seem as normal as growing up, but when we look closer, we see that it’s a complex and often painful mystery. And it’s a mystery we must solve because aging poses a dramatic increase in our risk of having every chronic disease. The major risk for all types of cancer is aging, and so is the major risk for diabetes and Alzheimer’s. We have a hundred- to thousandfold greater chance of dying from aging than of dying from other risks like obesity or high cholesterol.
Everyone talks about cholesterol contributing to cardiovascular disease, but it’s only a threefold risk, whereas aging is a thousandfold risk for dying from cardiovascular disease. Cardiologists have argued that cardiovascular disease is just accumulation of plaque over time, but we know from autopsies of people in their twenties that plaque can start to form early on. For the first forty or fifty years of our lives, we can deal with those plaques, and they are actually dynamic—forming and going away. After age fifty, we start to lose the ability to control plaque accumulation because some of the biological processes that controlled it, decline. Some evidence suggests that a series of changes or mutations makes an organism likelier to die from loss of cells or from cancer, other evidence suggests it’s an increase in inflammation levels or oxidative damage that causes aging, and still other results suggest that aging occurs when our bodies lose the ability to activate the stem cells that keep our other cells healthy. All these theories have merit, but none of them alone is enough. To the degree that they’re true, they all drive aging together.
Most chronic diseases are united by one primary cause—the biology of aging itself. While there are genetic and environmental bases for many age-related diseases, aging increases our chances of contracting them more than any other factor alone. Aging is the main reason for the global epidemic of chronic diseases. The World Health Organization (WHO) estimates that these age-related diseases are responsible for about 70 percent of the global death rate and 80 percent of U.S. Medicare costs, which the WHO projects will cost the global economy more than $30 trillion by 2030. While life expectancy in the United States ranges from 74.7 years for West Virginians to 81.3 years for Hawaiians, research shows that the average American enjoys only 67.7 healthy years. So nobody can logically argue that we don’t need to accelerate our ability to increase health span—the span of good health. But based on health-adjusted life expectancy (HALE), the United States is not doing well with this. In fact, we’re doing worse than the European Union and ten other countries ranked in a report by the Aging Analytics Agency, coming in dead last after China. The three-hundred-page report points out that this is despite the fact that, among developed countries, the United States spends the most on health care per capita, at $9,892. Unfortunately, that number is predicted to grow an average of 5.5 percent a year through 2026, and if that happens, by 2027, health care spending will represent 19.4 percent of gross domestic product.
If we don’t make some dramatic changes in how we approach health and instead continue to treat one disease at a time, the best we can hope for is exchanging one disease for another. Making matters worse, these age-related diseases tend to accumulate and lead to functional decline. Often, surviving one onslaught only buys time for another onslaught. We’ve all heard about someone who had a stent installed or had coronary bypass surgery to prevent a heart attack and then died from a different chronic disease a few years later. Treating one disease at a time or targeting just one organ rather than targeting aging is a miserable approach—and it’s not working. When I started on the quest to understand aging, most of the research had been focused on the causes of aging, so I decided to approach the problem from the opposite side and find out what delays it.
When I entered the field, scientists like George Martin, one of the fathers of modern gerontology and a mentor to me, were trying to solve the mystery of aging predominantly by studying children with progeria, rare syndromes that age people far faster than what is considered normal—in effect, their biological age races ahead of their chronological age. But although those studies were extensive, the findings didn’t unlock many secrets of aging. So I thought that instead of studying people who age rapidly, we would study centenarians—those lucky folks who appear to be far healthier and more youthful than their years would predict. Centenarians are extraordinary because even as their chronological age ticks relentlessly forward, their biological age hangs years or even decades behind.
Studying centenarians led us to ask many questions, but the biggest one was:
Can we prevent or delay aging?
The answer is yes.
We still have a lot to learn, but the promise I can make is that help is on the way, thanks in part to the secrets of “SuperAgers” like the centenarians in our studies at the Albert Einstein College of Medicine’s Institute for Aging Research, which I founded. For them, the outlook is entirely different—all the chronic diseases are delayed. We experience old age and illness as one and the same thing, whether it’s diabetes or Alzheimer’s, Parkinson’s or cancer, but at seventy, the SuperAgers have twenty to thirty more mostly disease-free years ahead of them. My research team and I are on a mission to find out how these people are living such long lives in such remarkable health. Each time we unlock one of their secrets, we explore how we can use what we learned to benefit everyone else.
What Makes SuperAgers Stay Healthy?
Many centenarians pass the hundred-year mark almost effortlessly. Whereas most people are ill for an average of five to eight years prior to death, centenarians tend to maintain most of their abilities and are ill for only about five to eight months before their deaths. While we expected many of the centenarians we studied to be diagnosed with cardiovascular disease, Alzheimer’s, and Parkinson’s at higher percentages, they weren’t. That said, it’s important to clarify that centenarians’ bodies are not young. Many of them have some limitations like poor eyesight or hearing, some have less mobility than others, and arthritis is common. But the major diseases are delayed, and at the age of their retirement, many of them were not seeing a doctor and had no medical expenses. Surprisingly, the health care costs of the average person who lives past one hundred are only 30 percent of those of the average person who dies in their seventies.
THE ABCS OF DNA AND RNA
DNA—deoxyribonucleic acid—is a molecule made up of two chains (a.k.a. polynucleotides) that carry the genetic instructions for growth, development, functioning, and reproduction of living organisms and many viruses.
RNA—ribonucleic acid—is a large molecule essential to the coding, decoding, regulation, and expression of genes.
Nucleotides are the building blocks of nucleic acids.
Nucleic acids are the small molecules essential to all forms of life.
Gene expression is the process by which the instructions of the DNA are translated to a protein through “messenger” RNA (mRNA).
The DNA alphabet consists of four letters, each of which represents a type of nucleotide:
Studying SuperAgers, people who are still living independently by age ninety-five, based on their DNA and other biological factors, is central to understanding the blueprint for how we all can age more slowly and maintain our good health. By discovering what makes these people so special, we’re discovering the real secrets of aging for the first time. SuperAgers largely sidestep the diseases that plague their peers—diabetes, cognitive decline, cardiovascular disease, Alzheimer’s, and cancer—maintaining vibrant lives that may slow down but don’t dim. They’re successful business leaders, musicians, and artists living independently into their late nineties and older. They help to raise their grandchildren, travel the world, learn new skills, and live full lives far longer than the rest of us. When they do contract debilitating diseases, it happens much later in life—sometimes two to three decades later than for most people and for a very compressed period of time.
We might theorize that these people derive all these benefits because they have healthier lifestyles than the rest of us, but that’s not the case. Instead, many of them break the health rules that the rest of us need to follow. Nearly 50 percent of the centenarians in our study are overweight or obese, nearly 50 percent smoke, and fewer than 50 percent do even moderate exercise. Remember the Kahns? When I asked Helen, who lived to 110 and smoked for more than ninety years, “Didn’t any of your doctors tell you to stop smoking?” she said, “Sure, but all four of those doctors died.”
Demographers estimate that for most people, genetics are responsible for about 20–25 percent of aging and the environment is responsible for the rest. But the statistics are vastly different for centenarians, whose genes are about 75–80 percent responsible for how they age and the environment accounts for only about 20 percent. That’s why we’re so determined to unlock their secrets. Doing so can give us insight into providing everyone with the same protections from aging that they enjoy.
Besides being medical marvels, these amazing people have made the most of their “extra years” by remaining engaged with life and dwelling on the positive. Every SuperAger I’ve met has interesting stories to tell and pearls of wisdom to share, no matter how humble they might be about sharing them. They make me look forward to the day when all our elders can be engaged members of society well into their nineties and beyond. At Einstein, we are determined to make that happen sooner rather than later.
The idea to look for the secrets of longevity in centenarians was exciting and promising, but figuring out how to design and conduct the study was devilishly complicated. How could we study a population that had no living control group? And what should we be looking for?
When we started the Longevity Genes Project in 1998, we had three distinct hypotheses about what made centenarians so special genetically. One was that the centenarians had a perfect genome, one without any variants or other errors or imperfections in the sequence of the genetic code of DNA, allowing them to grow and age in the most optimal way. The second hypothesis was that centenarians had very healthy lifestyles and environments. Our third hypothesis was that centenarians had all the same variants in their DNA as the rest of us but were being protected from their negative effects by other variants in the sequence of their DNA. If that was the case, though, how could we discover those protective variants?
MUTATIONS AND VARIANTS
A mutation is a natural and permanent change in the sequence of the chromosomal DNA. Mutations are rare. Only about one person in one million has a mutation that causes a phenotype of sickness, or for centenarians, extended health.
A variant is a mutation that has spread into the population and therefore has become more common.
Geroscientists are looking at rare and common variants associated with exceptional longevity in our centenarian population.
Common changes that occur across the DNA in individuals are known as variants, some of which are associated with and may cause diseases. If the variants are rare, they’re known as mutations. Each variant or mutation gets a single nucleotide polymorphic (SNP) number that identifies it in the sequence of the genome.
As for finding answers, strong data suggests that exceptional longevity runs in families—people with a centenarian parent are about ten to twenty times likelier to become a centenarian or have a sibling who will make it to one hundred than people who don’t have centenarian parents. For that reason, it made sense for us to study exceptional longevity genetically. And because it’s rare, it’s easier to find genetic differences in a group of centenarians than in a group of people with common illnesses like diabetes or hypertension. When the human genome was sequenced, we looked for common variant differences between people with diseases and people without diseases, but we were disappointed by how little we found. Despite the great expense of the technology at the time, the genetic information we got usually explained less than 5 percent of the contribution that these common variants made to each of the common diseases. This happened because most of the DNA we have is not coding for the genes that make up the less than 30,000 proteins that make up our biology. So about 90 percent of the variants are overrepresented in noncoding areas and underrepresented in the regions that code the exact sequence of a protein. In other words, there are more variants near the genes, between the genes, and between the coding sequences of the genes than in the coding sequences of the genes themselves. We were more interested in finding genetic variants in the coding regions of the genes, but at that time, we knew there was no chance of getting funded because the genetic testing was extremely expensive and had major quality-control issues. Furthermore, to study this in an unbiased way, we needed to design a scientific study that was solid enough to get funding. In particular, we needed to figure out how to isolate what made centenarians genetically different without being able to compare them with their peers who had died decades earlier.
I should point out that by no means was I the first scientist to be interested in centenarians. But in the quest for genuine secrets for health span and longevity, I put together the first group to study centenarians’ biology and genetics, and we launched the Longevity Genes Project the year after Madame Jeanne Calment died at the age of 122. Madame Calment, who became a celebrity of sorts, stirred a lot of interest in centenarian studies because she was known for being “young” well into her later years. Calment was born in 1875 in Arles, France, and lived there for her entire life. Arles is known for inspiring Vincent van Gogh’s paintings, and Calment met Van Gogh when she was twelve. When she was twenty-one, she married a second cousin and went on to enjoy a prosperous life filled with physical activity, including fencing, swimming, tennis, cycling, and mountaineering. Her husband died in 1942 when she was sixty-seven, but that didn’t slow her down. She continued to participate in all the activities she’d enjoyed with her husband for decades, including riding her bike around Arles until she was one hundred. She reportedly ate two pounds of chocolate every day and credited her olive oil–rich diet for her calm disposition and her long life. “That’s why they call me Calment,” she used to say. (Calm in French is calme.)
When she was ninety, a notary by the name of Andre-Francois Raffray made her an offer to buy her apartment, with the condition that she could live there until she died and he would pay her 2,500 francs a month until then. Not only did Calment outlive Raffray, but the payments she’d received amounted to more than twice the apartment’s value. “In life, one sometimes makes bad deals,” she reportedly said of Raffray’s ultimately losing proposition. Calment lived on her own until she moved into a nursing home at age 110, and she remained physically active until she was injured in a fall when she was 115. But even after that, her mind remained sharp.
It is possible that other people have reached age 122, but validating such claims is difficult. I was on a panel that heard the twenty-five pieces of evidence that validated the findings for Madame Calment’s age, and you can be sure that the panel was very thorough, because understanding our maximal capacity for life span is essential for aging research. Some disagreed with Calment’s claimed age, but in the paper disputing her age that I reviewed, no substantial evidence was provided. One argument was that the physician who saw her on her one hundredth birthday commented that she looked twenty years younger than her age. But at Einstein, we had collaborated with Anne Chang, associate professor of dermatology at Stanford University School of Medicine, on a study of skin-aging genes in which we’d objectively assessed the skin age of our centenarians and found it to be about twenty-four years younger than their chronological age on average. So of course Calment looked younger than her age. I’m certain that the unsubstantiated “conspiracy” theory that she was actually her daughter won’t prove out. There’s no way that we were off by even a year, let alone two decades.
So, comfortable with using 122 as our high-water mark, I began thinking about which centenarians we should study in the Longevity Genes Project and how to find them. Although the fact that exceptional longevity is rare and tends to run in families makes centenarians a good phenotype—or a set of observable physical characteristics—for genetic studies, this phenotype becomes a disadvantage when it comes to finding enough people nearby to conduct a large study. When we started the study, it was estimated that only one in ten thousand people was a centenarian. Today, the number may be closer to five in ten thousand thanks to life-extending hip and knee replacements, artificial limbs, and pacemakers, but even though their longevity isn’t entirely “naturally occurring,” you still need some genetic help to make it that far. And while the expanded pool helps some, five people in ten thousand is still a pretty small number.
The Icelandic population is the best population in the world for genetic studies because there are fewer than half a million Icelandics, and they are all descendants of five Viking men and four Irish women—you can’t get much more interrelated than that. So the chances of finding genetic differences that account for any disease would be very high in that population compared with the chances of finding them in New York City. Genetically diverse populations create a lot of genetic noise in studies, which makes it more difficult to find genetic causes. But unfortunately, I needed more centenarians than the Icelandic population has, and besides, Iceland is a long commute from the Bronx, where the Einstein Institute is located.
Curious about how many centenarians were living close by, I checked the records at the voter registration office. At that time, the population of the Bronx was just over six hundred thousand, so I estimated that I could recruit fewer than a hundred centenarians in the borough. Imagine my surprise when I saw that close to five thousand centenarians were living in the Bronx! When I looked closer, I saw that many of them were allegedly 150 years old or older, and I smelled a voting scam. The practice of using the names of dead people to vote is just one example of why it can be hard to verify someone’s true age, and the challenge is worldwide. The Japanese are the longest-living people in the world, but some families wait for years before they announce the death of parents so that they can continue to collect social security. So while the average life expectancy is eighty-four for Japan’s population, we cannot always trust the reported ages of individuals, in particular when they are so old.
After exploring a few other dead ends, it occurred to me that I should recruit only Ashkenazi Jews (AJs) for the study because of the homogeneity of their population. They have remarkably uniform genetics, which resulted from discrimination, persecution, isolation, inbreeding, and population expansion that followed “bottleneck” periods when many died. For these reasons, their DNA gives us an advantage in identifying genetic diseases. An example of their genetic closeness is the prevalence of Tay-Sachs disease among their population. About 3.5 percent of Ashkenazi Jews in the United States are carriers of the disease, compared with 0.33 percent of the general population. When a particular gene mutation is inherited from one of the parents, the offspring carrying the disease is called heterozygous and does not have symptoms of the disease. If a particular gene mutation is inherited from both parents, it’s homozygous and results in the manifestation of Tay-Sachs. About one in 3,600 Ashkenazi Jews in the United States have the disease, compared with one in 320,000 in the general population. With the advantage of such clearly drawn lines between heterozygosity and homozygosity, we started looking for links between these conditions and longevity.
We don’t think Ashkenazi Jews are more or less likely to become centenarians than people in other populations, but we know they share many common ancestors—40 percent of all Ashkenazi descend from just four mothers, according to markers in the DNA of their mitochondria (which is almost always inherited from mothers only). Because, like the Icelandic population, they are so genetically close, the sequence of their DNA is less noisy and much easier to study than the DNA of a genetically diverse population. Another factor in our decision was that Ashkenazi Jews in the United States are similar in socioeconomic levels, and we know that education and income have a major influence on health span in this country. Last, most of the Ashkenazi Jews in America live in the New York area and between Boston and Washington, D.C.—places my study could reach more easily than Iceland.
Our first participants in the Longevity Genes Project came to us courtesy of people we knew, and we used passports, birth certificates, and driver’s licenses to verify age. Einstein chief of endocrinology Norman Fleischer, who had recruited me to the institute, and his wife, Eva, introduced me to her mother, who was 102. Norman was smart, knowledgeable, and one of the best clinicians I’ve ever met. He was a dear father figure to me, so it meant a lot to me that he was the one who connected me with one of the first centenarians in the study. Next, Ruth Freeman, a women’s health endocrinologist and a great educator, introduced me to her mother and aunt, who were both over the age of one hundred.
After that, word of mouth led us from one centenarian to another, and we were surprised by how many of them knew each other. Then, shortly after we met the Kahn siblings, we started to get publicity, including an extensive article in New York magazine, and our numbers started to grow. People called us to say that their relative or neighbor was a centenarian, and we also received help from Jewish homes for the elderly and the Dorot Foundation, a wonderful nonprofit organization that helps to alleviate social isolation and provides services for older adults.
Designing a Study Without a Control Group
Figuring out how to set up a control group for the study was another challenge because most of the centenarians’ peers had been dead for decades. The first centenarians in our early studies were born between 1895 and 1910, when the average life expectancy was only about forty years because so many people died from childhood diseases. The people who made it to forty had a life expectancy of a little over sixty. So the centenarians lived forty years longer than their friends, who would have been the real control group. For a controlled study, we’d need to compare the DNA of centenarians with the DNA of unrelated people who were born and shared the environment at the same time as they had but had died. Grave digging wasn’t an option, so we had to find another way.
And while we looked for it, we also grappled with what we should measure in the centenarians’ blood samples. My line of thinking was that analyzing anything but their DNA at that age might be misleading. For example, assume that we’re measuring something in the blood of centenarians and we find that they have significantly higher levels than the normal value. On one hand, it could have contributed to their longevity, but on the other hand, since any given centenarian has almost a 30 percent chance of dying in the next twelve months, the high levels could also have been predictors of death.
With those considerations, we decided to recruit not only centenarians but also one offspring of each, because the offspring have half of the longevity genes and the phenotype of their centenarian parent. So if something measures high in centenarians and it’s also high in their offspring, it probably has something to do with their longevity. Another benefit of including the offspring is that we can isolate the longevity mutations and track them as they’re passed down through the generations. But the most important reason to recruit the offspring is that while we could not create a control group for their parents, we could create one for them.
Initially, the control group was composed of the spouses of the offspring if they were Ashkenazi Jews with all four grandparents being AJs. None of the spouses in the control group had grandparents who had lived longer than age eighty-five, so we knew they didn’t have longevity in their families. Since the spouses were part of the homogeneous population, lived in the same house and community as the offspring, and had similar health habits, we determined that they were a valid control group.
Our next step was to submit our plans for the study to the Institutional Review Board (IRB), which protects the rights and welfare of people who participate in research studies. The IRB is responsible for reviewing all proposed research studies that include human participants, and it has the right to approve, disapprove, oversee, and require changes in all research that is under its jurisdiction. So we sent our study proposal to the IRB, and I explained that we would be looking at centenarians and their children. The next day, the proposal was back on my desk with a note: “For children, you need different forms.” But of course, we were talking about eighty-year-old children, and we decided that the term offspring would probably cause less confusion.
Today, the control group consists mostly of AJs who are neighbors of the centenarians’ offspring rather than spouses. We included these people in the control group because the reviewers of our grants were concerned about assortative mating, which refers to a pattern of choosing mates in which people with similar traits and habits mate more frequently than we’d expect (under a random mating pattern). An obese person is likelier to marry an obese person, a vegetarian is likelier to mate with a vegetarian, and a smoker is likelier to marry a smoker. This tendency carries over into income and education levels, too. In the United States and to a lesser extent in other countries, when you marry, you choose a lot of the health issues that you may have later. We thought mates made a better control group than neighbors, because mates share the same environment and tend to have similar habits and diets (although, granted, one could certainly eat significantly more than the other). And we argued that spouses of the centenarians’ offspring didn’t marry them based on the longevity of their parents. For one thing, their parents weren’t centenarians when the offspring married, so they didn’t have that information at the time. But we rolled with the punches and recruited neighbors in addition to the mates, and our data shows that the two control subgroups are genetically similar.
Meeting Our First AJ Centenarians and Their Offspring
I met with the first several centenarians myself, and one of the questions I asked them was whether exceptional longevity ran in their families. It turned out that it usually did, with many of them saying they had family members who had lived to be one hundred or older. This supported our theory that exceptional longevity is primarily based on genetics, and so did the centenarians themselves. When asked why they think they live longer, their number-one response was genetics. None of this surprised us, though, because Tom Perls, director of the New England Centenarian Study at Boston University, Paola Sebastiani, genetics professor, and other investigators had already shown that exceptional longevity is often inherited.
Besides talking at length with the first centenarians, I examined them and took their blood. By the time the study was officially under way, I had used that information to create a questionnaire adapted from one that had been validated in large studies, but trying to figure out what to ask before that questionnaire was in place provided some challenges. For example, colleagues and friends had all sorts of ideas about what I should ask, but an overwhelming number of them thought there was a connection between longevity and napping. So I added napping to my list of questions, and the next time I interviewed a centenarian, I asked him if he napped.
“I nap every afternoon,” he said.
Wow, I thought, we might be onto something. “Did you nap every day last year, too?”
He thought about it. “No.”
“How about the year before that?”
He shook his head. “I don’t think so. I don’t remember. But I remember taking naps the year I retired.”
If he had retired a few years before this conversation, that might have been an indication of a pattern, but he’d retired more than twenty years earlier. So while centenarians may have once had habits that contributed to their longevity, we cannot rely on their memories to be accurate, and their habits may have changed from year to year. But we can rely on our lab results and the health histories that we take when we meet each centenarian and one offspring.
Meeting the centenarians quickly became a highlight of my work. I could easily sit with them all day to hear their stories, insights, and wisdom, carried from my grandparents’ generation. Many members of that generation were Holocaust survivors, including my uncle Ervin, who suffered in six different concentration camps before World War II ended. Ever since I was a young boy, I was impressed by stories about my uncle Ervin, as well as the stories he told me about my family that my mother—another survivor—wouldn’t talk about. Now here I was listening to the stories of other people who were part of the same generation and had experienced some of the same events. They all made indelible impressions on me, but the commonalities I shared with Benjamin were especially moving. At 104, Benjamin was alert, charming, and thoughtful. He had been born in 1898 in a tiny settlement in Israel called Rishon LeZion. Settled by Russian Jews, it was the second Jewish farm settlement in Israel. When I met him in 2002 in New Jersey, he said the settlement was located not far from Sarafand al-Amar, where the British army had built the biggest transportation base in the Middle East.
“Sarafand?” I asked.
“That’s where I served!”
He had served with the British army, and I had served more than fifty years later with the Israeli army, and we discovered we’d even lived in the same barracks. For Benjamin, having a job as a truck driver at the base and being able to live in the barracks had been a godsend. For me, the time I spent at Sarafand had also been a godsend, though in a very different way. Over the course of the three years I spent with the Israeli Medical Corps in the 1970s, I progressed from a medic to an instructor of medics to a chief medic to the army’s chief medical officer. I went from bunking with fifty other soldiers to having my own office, car, and secretary and doing inspections by helicopter. A lifetime career in three years.
I realized that the man pouring coffee across the kitchen table from me not only had had a life that preceded the state of Israel but had also been born before radio broadcasting, penicillin, and air travel. And because he had endured and continued to thrive, our lives were now intertwined. He was a pharmacist and I a doctor, both of us living outside New York City, both of us far from our original homes. How much we had to say to each other and learn from each other. Nothing separated our stories but time, and as we talked, a century contracted to the size of the kitchen table. This, I thought, this is what it should be like to age. We should all be so lucky!
With that goal in mind, it was time to start testing some hypotheses.
A Perfect Genome?
In light of the disappointing results we got from the very expensive process of human genome sequencing, we decided to focus on the genes that we thought were the best candidates to be involved in aging. To create a list of these “candidate genes,” we measured several blood components in families of centenarians and found out about their biology. With gene sequencing, we could find out if any of the centenarians’ variants we found differed from the variants of members of an unrelated control group.
To test the hypothesis that centenarians had a perfect genome, we conducted the entire genome sequencing in our first forty-four centenarians. After performing the sequencing, which consists of reading the sequence of approximately 3.2 billion nucleotides that make up the genome of each individual, we obtained information from a database called ClinVar, an important library that compiles the background on the twenty-thousand-plus variants that are the probable causes of all disease. The data comes from people who are healthy and those who have diseases, and we use it to try to find the causes of age-related diseases and illnesses. We wanted to know whether centenarians exhibited any of the determinants of diseases, and our theory was that they did not.
We were stunned by what we found. The forty-four centenarians we studied didn’t even come close to having perfect genomes. Between them, they had more than 230 variants that ClinVar identified as most likely to cause age-related illnesses, such as Parkinson’s disease, Alzheimer’s disease, inflammatory diseases (including heart disease), and cancers. They exhibited an average of five to six variants that should have caused disease but didn’t. Most striking, two of the centenarians had variants that are a major risk for Alzheimer’s (APOE4)—the textbooks say they should have been suffering from dementia at age seventy and dead at eighty—but they were alive and mentally well at one hundred plus! As for the million other variants we looked at, on average, the centenarians had as many variants that are genetically associated with age-related diseases as the control group had.
So with our first hypothesis shot down, we turned to another.
Centenarians’ Interactions with Their Environments
A one-hundred-year-old Japanese artist is being interviewed for a newspaper piece about working long after the average retirement age.
“What’s the secret of your longevity?” the reporter asks.
The artist finishes cleaning his paintbrush. “I don’t know, but I really love fish. I eat it twice a day, and so does my father.”
“Your father? How old is he?”
“He’s 125. He eats fish three times a day. Would you like to meet him?”
“Sure. Where is he?”
“He’s helping my grandfather herd the cattle.”
“Your grandfather? I suppose he eats fish four times a day.”
“No, Grandfather hates fish.”
As with most jokes, there’s a lot of truth in this one. Just when you think you’ve isolated the cause of something, new information complicates the picture. While the discussion of nature versus nurture is ongoing, I was starting to see centenarians’ longevity as a cooperative effort between nature and nurture or, more specifically, between genetics and environment. Studies correlating the age at which the parents died and the age at which their children died seemed to suggest that the genetic influence on aging accounts for only about 20 percent of the variations in life span and that environment is responsible for the rest.
But then again, I could see a problem with this low assessment of the genetic contribution in my own family. My grandfather Dov had a heart attack and died at age sixty-eight, while my father, David, had a heart attack at the same age but didn’t die till sixteen years later, thanks to bypass surgery. So the relationship of mortality between parents and children changed not because of a difference in aging (they both had heart attacks at the same age) but because of the change in the environment, which in this case was medical intervention. Meanwhile, studies of identical twins who were separated early in life and had different levels of health and different diseases in midlife suggest that genetics account for about 25 percent of the variations in life span. That means that even if you have genes that increase your risk for type 2 diabetes, if you’re physically active, eat healthy foods, and manage your stress, you may never develop the disease. So the effects of genes and the effects of environment are not easy to isolate, but as we learn more about genetics’ share of the responsibility, we can plan better strategies to protect ourselves from the environment.
All that said, though, all bets are off when it comes to people with exceptional longevity. Other studies suggest that for people with such long life spans, genetics may deserve up to 80 percent of the credit. We still had questions about how much environment might have added to our SuperAgers’ longevity, though, so we began a study to assess their lifestyle factors.
The study included 477 Ashkenazi Jews who had been living independently as of ages 95–109. Our nurse, Bill Grainer, collected data on body measurements and administered study questionnaires to gather information on lifestyle factors. In addition to asking them about their habits, we asked them why they thought they lived so long, and all in all, their responses were not what I was expecting. Here are the top ten reasons they gave us:
#10: HELPING THOSE IN NEED
Many of our 477 SuperAgers volunteered and worked in service of others throughout their lives, even past the century mark. At age ninety-five, Fanny Freund serves as a vital link between the generations as a volunteer for the Dorot Foundation, which creates mutually beneficial relationships between seniors and younger people. During visits facilitated by the foundation, she hosts students at her home for discussions of her family’s experiences during the Holocaust and her time on a kibbutz in Israel. Another SuperAger, 104-year-old Lilly (Brock) Port, wrote Access: The Guide to a Better Life for Disabled Americans (Yonkers, NY: Consumers Union, 1978), one of the first books to empower the disabled with economic information specific to their situation, during her time as director of consumer education at the Department of Consumer Affairs. She also provided education by way of a consumer affairs radio show. And Irving Kahn served as a trustee emeritus for the Jewish Foundation for Education of Women and founded the New York City Job and Career Center, which helped prepare high school students for the workforce.
#9: BELIEF IN GOD OR SPIRITUALITY
I assumed that a good many of our SuperAgers would mention God or spirituality as a reason for healthy longevity, because when we ask them how they feel, they often say something like, “I’m feeling good, thank God.” But only 6 percent included spirituality among their reasons for longevity. That said, though, a significant number of our SuperAgers still keep the faith. Fanny is among those who regularly attend synagogue and remain active in their spiritual practice. She says that when her husband of sixty-three years was alive, the synagogue kept them so busy at their separate duties and activities that they rarely saw each other except nights and weekends.
We weren’t surprised that luck made a showing on the list, but we were surprised that it placed so highly. Even at age ninety-seven, chemist Morton Rosoff—a scientist—largely credits luck for his longevity. And that’s coming from a SuperAger who’s been defying the odds from the start. Six weeks after Morton was born, he came down with pneumonia and doctors didn’t expect him to survive, but he recovered, and in the nine-plus decades since, he’s also recovered from heart bypass surgery and a pulmonary embolism that involved such a large blood clot that, again, doctors considered him a lost cause. Though he acknowledges that it’s “not very Einsteinian,” he seems to speak for many of our SuperAgers when he says he thinks life span is largely a matter of chance. But Morton also happens to have an older sister, one-hundred-year-old Dorothy, so he may have more than luck on his side.
#7: KEEPING BUSY AND ACTIVE
Forty-seven percent of men and 43 percent of women said staying busy was a reason for their longevity. And for some, working was part of the equation; 20 percent of the men and 8 percent of the women said they thought it played a role. The life of Harold Laufman may be the strongest argument for the “staying busy” hypothesis. Harold, who died at age ninety-eight, was a modern-day Renaissance man who packed his “extra years” with doing. When I asked him to list his interests for me, the list he came up with was a very short one: “Everything.” Besides his career as a surgeon, he was an accomplished illustrator and painter, and in his eighth decade of life, he began a career in bioengineering. For the next twenty years, he approached life the same way he had for much of his first seventy—by balancing career with all his other passions and doing his best to explore “everything.”
The subject of engagement with life was a favorite topic of discussion whenever I saw Harold: Was his level of engagement the reason for his longevity, or did “good genes” simply make it possible for Harold to thrive for all those years? Whatever the answer, Harold and many other SuperAgers make a convincing case for the benefits of making the absolute most of every day.
#6: NOT SMOKING AND MODERATE DRINKING
Only about 40 percent of the men and 60 percent of the women said they avoided smoking and believed that this contributed to their longevity. Like his older sister Helen, Irving was a longtime smoker, not kicking the habit until he was about fifty, when he quit to set an example for his children. And many of the SuperAgers who did not smoke had spouses who did, but the secondhand smoke did not appear to have negative consequences for them. Morton’s wife, Anne, for example, was a smoker throughout their fifty-four-year marriage, adding to the considerable odds against his exceptional longevity. But those decades of being exposed to secondhand smoke have not taken a detectable toll on Morton.
As for alcohol consumption, we don’t know how much protection the SuperAgers have against its effects, because only 24 percent of the men and 12 percent of the women reported drinking alcohol daily.
#5: SOCIAL OR FAMILY SUPPORT
The fact that SuperAgers’ fifth most common reason for exceptional longevity was social or family support didn’t surprise us, because all the people in our study reported having layers of supportive family members in addition to outside help from social service agencies and in-home aides. Evelyn Edelstein, for example, says she’s blessed with three attentive sons, five grandchildren, and two great-grandchildren, and at age ninety-nine, she had the opportunity to see her granddaughter graduate from Yale. She also has friends who range in age from the seventies to early nineties, and she sees all of them often. Meanwhile, in addition to her synagogue family, Fanny sees her sons and their families regularly, and judging by the lift in her voice, FaceTiming with her grandchildren and seven-year-old great-grandson—“a lovely little guy” named Lev—is her greatest joy. “Oh my God, that’s the best—I love FaceTime—because he’s so cute.”
As important as family and friends are to our SuperAgers, it’s possible that it wasn’t ranked higher because most of the people in our study have lost the most influential partner of their life and their best friends.
#4: POSITIVE ATTITUDE
After enduring significant hardships early in life, my wife’s grandmother Frieda emerged from it all with an unshakable optimism, and that kind of positive outlook is a hallmark of many of our SuperAgers. After her family moved to the Bronx from Poland when she was sixteen, she spent the next forty years living close to the poverty line like many immigrants, but she ultimately prevailed, living to age 102 and finding joy all along the way. “No matter the difficulty that one encountered, she always gave you the belief that it’ll get better soon,” her son (and my father-in-law) Jerry Rubenstein says.
Irma Daniel, who also moved to America from Europe with her family, demonstrated the same kind of emotional resilience. Having fled Germany in response to the attacks on Jews initiated by Adolf Hitler, her family greeted the challenge of starting their lives over with gratitude and optimism. “This was, for us, a fantastic beginning,” she told me with the smile that never seemed to leave her face. Even in her eleventh decade of life—she died at 106—she was grateful for the quality of life she enjoyed. “I think it’s wonderful to get that old and have all your faculties,” she said. In our study, 19 percent of the SuperAgers said they think this positive way of seeing the world and their lives is a reason for their longevity.
#3: PHYSICAL ACTIVITY
Considering that four-star nutrition isn’t common among our SuperAger study participants (see #2), I thought that maybe they were exercising enough to make up the difference, but only 20 percent of them (more men than women) believed that physical activity played a role in their life span. And even though physical activity was the third most common answer they gave to explain their extended life spans, their histories showed that not many of them were especially active. Frieda was a perfect case in point. “She didn’t believe in exercise,” Jerry says, but she lived to age 102 anyway, the same age at which her father died.
There are exceptions, of course—like Jerry, who’s part of our study because he is the offspring of a centenarian. At age eighty-nine, he still plays two sets of singles tennis a day and appears to be in great health. And Lilly, who makes it a practice to walk up and down the stairs of her home sixty-five times a day. Speaking of steps, she also climbed the three-thousand-plus steps at Machu Picchu during a recent visit. And she’s a regular at her gym, where she is often found walking a treadmill, riding a stationary bike, working with weights, or taking a tai chi class. “You have to be active—exercise and walking, lots of walking,” she says when asked for some tips for living a long, healthy life. “And skiing and bicycle riding and…” And the list goes on.
This response surprised me because the SuperAgers’ diets frequently included fatty meats, schmaltz (rendered chicken fat), and sweets. In fact, the only complaint I ever got about the trained nurse who administered the questionnaires was that he didn’t accept the high-fat baked goods that the SuperAgers had made for their meetings. I would get phone calls saying, “He was a very nice man, but why wouldn’t he eat a piece of my cake?” Once I explained to him that he needed to accept all edible gifts and that he was free to give them away to the first takers he ran into, I got no more complaints.
But whatever the larger truth is, we certainly have our share of SuperAgers like Lilly, who take diet very seriously. “I am not letting myself eat as much as I would like to, and I’m trying to stay away from fattening things,” she says. And for her, it’s been a lifelong habit, not just something she got smart about in her later years. At sixteen, she decided that she had put on too much weight, so she cut out the cookies and lost thirty pounds. And judging by photos taken throughout her life, she consistently kept them off.
#1: GOOD GENES
Despite all the external factors that might figure into longevity—the factors that the SuperAgers have control over and often do take control over—they believe that genes are the biggest determinant of life span. And of course, I agree. Remember that exceptional longevity tends to run in families, and that’s a strong indicator that environment and lifestyle can carry most of us only so far. In chapter 2, we will explore some striking genetic similarities among people with exceptional longevity.
Do as I Say, Not as I Do
Once we knew what centenarians thought was keeping them alive, we were able to look at how their opinions compared with their lab results and health histories. And yes, we were surprised again. The results of the lifestyle factor tests made it clear that it wasn’t healthy habits keeping the SuperAgers alive and well. Even though many of them gave credit to their diets and physical activity for their extended years, most of them weren’t living these beliefs at the time of the study, nor had they lived them during their early years. Based on the National Health and Nutrition Examination Survey (NHANES-I), they had mean body mass indexes (BMI) similar to the national average, but almost half of them had been overweight or even obese for most of their lives. Sixty percent of men and 30 percent of women had been heavy smokers for more than thirty-five years, and 20 percent drank alcohol daily for much of their lives. And fewer than half of them had been physically active over the course of their lifetimes—only 43 percent of the men and 47 percent of the women. The numbers for restricting calories were even lower: 21 percent of the men and 27 percent of the women. While plant-based diets are often credited with greater health and longevity, fewer than 3 percent of the SuperAgers in our study were vegetarians.
So much for healthy lifestyles getting credit for long lives! We were astonished that our study subjects had habits that were as bad as or worse than the habits of those in the control group. It was clear that as a group, people with exceptional longevity do not have healthier practices or habits than the general population. When we completed this study, the important takeaway for us was that our third hypothesis appeared to be correct—the SuperAgers were somehow being protected by genetic differences that the general population doesn’t have. But when the results of the study were published in 2010, the media put an inaccurate spin on the story, and so did many people who saw me interviewed for a network news segment.
Shortly after the interview, I was at a coffee shop when I was stopped by a middle-aged man who recognized me from the interview. “You changed my life,” he said. “I saw your interview when I was at the gym. My grandmother is one hundred years old, so I don’t need to exercise anymore.”
It got worse. Jay Leno, then host of The Tonight Show, said, “Scientists at the Albert Einstein College of Medicine—I don’t know where that is—showed that the secret for successful longevity is eating, drinking, and not exercising … And the good thing about it is that if you die anyway, you don’t care.”
Of course, our findings applied only to centenarians, and I made sure that I said that in every interview I gave, but people didn’t want to hear that part. Even for people who inherit longevity genes, I recommend a healthy diet and regular physical activity. What was ironic was that the media had a field day with this study and all but ignored the most significant discoveries we were making. The real news was our realization that something must be protecting the centenarians, some undiscovered genetic alteration that helps, not hurts. Something that keeps these wildly different individuals living longer and far better than the rest of us. We have already identified some of these defenses, and research aimed at using them in treatments is under way. (I’ll explain these in detail in chapter 2.) When we made this discovery about centenarians’ remarkable genetic makeup, it was the first key to unlocking how we age and how we can age later and better. By that point, the study had been under way for five years, and this was our first big win.
Copyright © 2020 by Nir Barzilai.