Spring Chicken Page 9
So far, he seems to be headed in the right direction: Even now, in his early seventies, he can drive a golf ball so far and so straight that guys half his age stop in midswing and go, whoa! In six months of 2013, he rode more miles on his bike than I did the entire year. More importantly, he had been able to throw away his blood-pressure pills, and now he takes no medications whatsoever. He is so healthy, in fact, that he too has been accepted into the Blast study, an accomplishment that made him no end of proud (and which reduced me to the low level of lying about my results in certain tests). All in all, he seems well on his way to sticking around long enough to spend every last penny of his grandchildren’s inheritance.
But as his concerned and congenitally skeptical journalist son, I couldn’t help but wonder: Will any of this stuff actually get him to a hundred?
Not according to Nir Barzilai. For more than a decade, Barzilai has been studying a cluster of Ashkenazi Jewish centenarians who live in the New York area, which has led him to some remarkable conclusions. An affable jokester with thick glasses and a babyish face, the fifty-six-year-old Barzilai could be an older brother to Mike Myers’s Austin Powers character, but beneath his schmoozy manner lurks the penetrating mind of a scientist on a mission.
He trained as an endocrinologist in his native Israel, and as a young physician in the 1980s he worked in clinics in Soweto, the poor black townships outside Johannesburg, South Africa. Even now, he still makes time to see patients, to keep himself grounded in the problems of real people. As his interest shifted to aging, he began wondering why most people become sick when they get older, while a select few seem to be immune. He decided to focus on the longest-lived among us, the centenarians. What makes them different?
Recruiting subjects was not easy, he found; elderly Jews tended to have complicated feelings about medical research. As the only child of parents who had survived the Holocaust, Barzilai was sensitive to their concerns. After spending countless Shabbats visiting synagogues all over the New York metropolitan area, he recruited more than five hundred elderly Jewish folk—they must be ninety-five or older to qualify—into his unique study of aging. (He also jokes that he will accept healthy hundred-year-old converts.) We’ll call them the SuperBubbes, using the Yiddish word for “grandmother,” since most of them are women anyway. Every year or so, he and his lab assistants subject the SuperBubbes to an array of physical examinations, cognitive tests, lifestyle questionnaires, and blood analyses, rather like an All-Star version of The Blast.
As a rule, he found, the SuperBubbes do not generally eat “healthy” diets and compete in triathlons, or engage in any other kind of recognizable exercise, for that matter. When they’re hungry, they’ll reach for a knish, not quinoa (sorry, Dad). Not only that, Barzilai has found that many of his SuperBubbes have actually smoked, some for decades, like Madame Calment. Nearly half were overweight or even obese, while less than 3 percent were vegetarian. Nevertheless, they ace their blood tests; in particular, they tend to have spectacularly high levels of HDL, or “good” cholesterol. “They have the best blood you have ever seen,” Barzilai says, excitedly. “Their blood is perfect!”
It’s not that Ashkenazi Jews have any special advantage in terms of longevity; on the whole, they don’t necessarily live longer than any other group of New Yorkers. Barzilai studies them because, for one thing, the strong cultural identity and long history of intermarriage among the Ashkenazim means that their genomes are relatively similar to one another. And that, he thinks, will help him pick out the “longevity genes” that he thinks differentiate the centenarians from the rest of us.
Barzilai’s theory was that the centenarians live longer for the simple reason that they age more slowly. That may sound obvious, but the interesting question is why. If you could somehow tease out which genes are actually responsible for their slower aging, then you’d be on to something major. “Most biology is about ways in which we are the same,” he told me. “This is an unbelievable opportunity for us to understand why the biology of some is different from others.”
Biologically speaking, men don’t get much more unique than Irving Kahn, whom I met one sunny November morning in his corner office, twenty-two stories above Madison Avenue. He was just finishing up with the Wall Street Journal and the Financial Times, and preparing for another day as head of his family’s investment firm, which manages some $700 million in assets. This was impressive, because Kahn looked to be well into his 80s, maybe 90—but in fact, he was 106 years old when we met. In three weeks, he would turn 107. “Thirty-seven people are coming to my birthday party,” he rasped. “I have no idea why.”
Perhaps they were coming for the same reason I was there: Because Kahn is one of the oldest men alive. He was born in 1905, three years before Henry Ford produced his first Model T. His family lived in Yorkville, on the Upper East Side of Manhattan, when it was largely populated by Polish and Hungarian immigrants. His father worked as a salesman, selling fine chandeliers to wealthy New Yorkers; oftentimes, he had to first persuade them to install electricity in their homes. Irving went to work on Wall Street in 1928, and ended up as a disciple of the legendary Benjamin Graham, the godfather of analytical investing. He lived through the Crash of 1929 in his first year on the job, and he considers Warren Buffett, whom he met and mentored after World War II, to be a mere pup. He is a survivor, a human version of The Ark, my family’s everlasting cottage on the lake.
To call Irving Kahn an extreme outlier is understating things. According to Barzilai, only one person in ten thousand makes it to the century mark, and three-quarters of those who do are women—despite the fact that very old women, in general, tend to have more health problems than very old men. “The women are less healthy,” he observes, “but they live longer.”
Indeed, this appears to be true at all stages of later life: One large cohort study of eighty-five-year-olds in Newcastle, England, found that men actually reached that age in markedly better functional health than women. One in three of the eighty-five-year-old men could perform every one of a list of seventeen different tasks of daily living, without help (things like brushing teeth and bathing), versus just one in six of the women. But the men still died sooner. “The men drop dead,” says Thomas Kirkwood, director of the Newcastle study, “while the women keep going.”
But very few women or men keep going much past a hundred, and for those who do, the risk of dying each year begins at one in three, and goes up from there. According to the Social Security Administration’s lifespan calculator, as of March 2014, Kahn can count on just 1.2 more years, statistically speaking [which, as of publication of this book in 2015, he is well on his way to beating]. But who cares about statistics? Kahn has already defied massive odds to become one of the oldest living Americans, pushing right up against the observed limits of male longevity, and yet he still goes to work each day. “There are how many people like him in the world?” asks Barzilai. “I don’t know, ten? Twenty, maybe?”
Not only that, but Kahn’s three siblings also lived past 100, including his older sister Happy, who passed away in 2011 at the age of nearly 110, despite having smoked for 95 of those years, à la Madame Calment. Irving himself had smoked for about thirty years, with no observable ill effects. Yet he seemed to regard his extreme age as a sort of mild annoyance, rather than the near-miracle that it is. He missed being able to walk the twenty blocks or so to work every day from his apartment on the Upper East Side, as he used to do until a building fire drill in 2002 forced him to descend twenty-two flights of stairs. His knees have bothered him ever since. He’s even more ticked off that, as he put it, “my eyesight is beginning to diminish.” How’s he supposed to read the Journal every day?
The stereotype of old people being kept alive by doctors and drugs, as they endure a living hell of medically prolonged infirmity, just doesn’t apply to centenarians like Irving Kahn, Barzilai insists. Oftentimes, he notes, when they come in to be examined for his study, “it’s their first time going to the do
ctor.” They’ve just never needed to go, but it may also help contribute to their continued survival, Barzilai thinks. “The oldest person in the world has steadily been getting younger,” he told me, “and I think it’s because the doctors have been killing them,” with unnecessary treatments like statin drugs for cholesterol. So my Christian Science relatives might have had a point, after all.
Because centenarians stay healthier for longer—another hallmark of slower aging—they are also a lot cheaper to keep around. Someone who dies at a hundred will rack up just one-third the medical bills, in their last two years of life, as a person who dies at age seventy, according to the Centers for Disease Control. Moreover, the seventy-year-old will have been sicker for much longer, an average of seven years of ill health at the end of life, versus less than two years for a centenarian. Public-health types call this the “compression of morbidity,” shortening the period of time during which old people are sick. This is a good thing: More lifespan and more healthspan, the opposite of the Struldbrugs. And, obviously, Irving Kahn has it pretty much figured out. But how?
He wasn’t about to divulge the secret, whether he knew it or not. His late-life fame and the attendant publicity—he’s been quizzed by TV journalists from all over the world—had hardened him into a wily, evasive interviewee. I was getting nothing. “Irving, am I correct in saying that you find your age is not particularly remarkable?” his grandson Andrew prompted him, in a louder-than-normal voice to compensate for his grandfather’s somewhat diminished hearing.
Irv nodded.
“And Bill, you might ask a question,” Andrew continued, “and Irv, you will do your best to evade the answer.” His tone verged on accusatory. “You will talk about a wide range of topics that have nothing to do with the question!”
Which is what Irv proceeded to do for the next two hours, leading me on a wild ramble from subject to subject. His interests are wide ranging: He remains a voracious reader, but only of nonfiction. Novels and poetry he regards as a waste of time, though he makes an exception for Shakespeare. My attempt to interest him in my ninety-seven-year-old grandmother, a looker who still puts on her pearls and makeup every day, fell flat; he’s still enamored of his wife, Ruth, who died in 1996.
We talked about the stock market, inevitably, and his never-ending search for undervalued businesses. He bought one company, a shipping conglomerate called Seaboard, for a few dollars a share, decades ago; now it’s at $2,600. Buy-and-hold makes a lot of sense as an investment strategy when you live to be 109 (as of December 2014). And it fits with one of Barzilai’s other findings, that his centenarians tend to have positive attitudes about life in general, in addition to their spectacular cholesterol numbers. As Irv put it, “The alternative is not useful.”
The fact that he goes to work every day, incidentally, is both a function of his extreme longevity—and also, in part, perhaps a contributing factor. On Okinawa, the famed Japanese “Blue Zone,” with the highest concentration of centenarians in the world, older people talk about the importance of ikigai, which translates as “a reason to get up in the morning”; in short, it’s your purpose. Irv’s ikigai is to find the next Seaboard. I was merely keeping him from his work.
He told stories about Ben Graham, and about his childhood experiments with the newfangled technology of radio. “Is that the Victrola?” his mother had asked. And so on like this, for two hours. He’d witnessed inconceivable changes during his incredibly long life, yet his own longevity was the one thing that he, of all people, could not explain. “You’re asking questions that have no good answer,” he growled at last. “I don’t think I can tell you what you want to know.”
“Irving is our poster child,” Barzilai told me, a few days later, “but biologically he is not interesting to me anymore, because he is at the end of his life. You really want to know—when he was fifty, sixty, seventy—how he was.”
The best he could do was to study the offspring of Irv and his fellow centenarians; he had found they, too, seemed to be aging more slowly than their peers. So Irving’s son Tommy, who came in to greet us, looked more like fifty-one than his actual age of seventy-one; and his grandson Andrew, who was in his thirties, would not have looked out of place in a Boy Scout uniform. And of course Irv’s three siblings had all made it past one hundred as well. The reason they all seemed to age slowly had to lie in their genes, Barzilai felt. I silently hoped I had received some DNA from my own long-lived ancestor, the ninety-six-year-old Puritan Elizabeth Pabodie.
The role of genes in determining longevity has been debated as long as we’ve known that genes exist. Studies of Danish twins have revealed that longevity is only 20 percent inherited, and 80 percent due to environmental factors. But that holds true only up until about age eighty-five. After that, heredity moves to the forefront, making up more like half the puzzle, if not more. As the evolutionary biologist Steven Austad (whom we’ll meet in chapter 7) puts it: “If you want to become a healthy eighty-year-old, you need to live a healthy lifestyle, but if you want to become a healthy hundred-year-old, you need to inherit the right genes.”
The fact that all four Kahn siblings lived so long is utterly unsurprising to Barzilai. “We are certain, there is no doubt in our minds, that exceptional longevity is mainly inherited,” he says. Just not in the way that he first suspected.
Barzilai initially believed that his SuperBubbes possessed “perfect” genomes, their genes optimally tuned for longevity. But as gene-sequencing technology developed, along with our understanding of the role of genes in disease, he was surprised to discover that the opposite was true: Many of his centenarians actually possessed some of the same crappy genes as the rest of us. He and his team sequenced the genomes of forty-four centenarians and found that nearly all of them possessed undesirable gene variants that are thought to promote nasty conditions, including heart disease, Alzheimer’s, and Parkinson’s. Yet none of them had gone on to develop any of those diseases. This led him to ask a different question: “How come people who should have dementia at seventy, and be dead at eighty, are living to a hundred?”
Instead of “perfect” genes, Barzilai decided, the long-lived must instead have protective genes, which prevent them from developing the usual diseases of old age. (Such ultraprotective genes may also explain why Keith Richards is still alive.) He decided to zero in on their cholesterol-related genes, because his centenarians had such excellent blood values and perfect cardiac health. He found that many of them had a specific gene variant that inhibits something called CETP, a molecule involved in cholesterol processing (it stands for “cholesterol ester transfer protein,” if you want to geek out on it). It’s complicated, but in general, the less CETP you have, the better; high levels of the protein are thought to lead to premature atherosclerosis. Centenarians with the CETP-inhibiting mutation not only had better heart health, and very high “good” cholesterol, but they also had a lower incidence of memory loss and dementia, according to a paper Barzilai and his colleagues published in JAMA.
This single gene, in other words, seemed to be protecting them from two of the Four Horsemen, heart disease and Alzheimer’s. Irving Kahn has the CETP variant, as did his siblings—along with roughly one in four of their fellow centenarians. But among sixty-five-year-olds, only one in twelve has the gene, which means that those with the gene are three times more likely to live to be a hundred than those without.
This finding dovetailed with research being done by the pharmaceutical companies, which were already desperate for a drug to replace the statin class of cholesterol-lowering medications, whose patents were all expiring. Merck and Pfizer and others raced to develop CETP inhibitors, which were meant to raise HDL (“good”) cholesterol. But so far, those drugs have not yet panned out, and some studies were stopped because too many patients died. (Merck has one still in Phase III trials, but it is the last survivor in the class.)
“They made a dirty drug,” says Barzilai, one that affected too many other targets besides CETP. He s
till believes that by finding more protective genes, and developing treatments that mimic their effects, it might be possible to extend healthy life for the rest of us—and “bypass the complexity of aging,” as he put it. The search is only beginning.
One other possible longevity gene had to do with IGF-1, the growth factor—which may not be so good for you, as we’ve seen in chapter 3. Barzilai found that his centenarians had relatively high levels of IGF-1, but oddly, their cells were actually resistant to it—also because of another gene variant. That is, Irv and his fellow oldsters aren’t just small because they are a century old; they have lived so long because they are on the smaller side, sort of like human Chihuahuas.
Yet the most striking thing about the longevity genes discovered to date is how rare they are, even in centenarians. Barzilai and other research teams have only been able to identify a handful of candidates, which he blames on the high cost of genomic-sequencing technology—and also on the relatively tiny number of centenarians worldwide. There are so few of them, relative to the rest of us, that it is difficult to single out specific genes as a statistically-convincing “cause” of their longevity. That could change, as sequencing becomes cheaper over the next decades. Barzilai and his team are working with GoogleX on a gene-sequencing venture, and in March 2014 geneticist Craig Venter jumped into the game, forming a company called Human Longevity, Inc., which promises to sequence forty thousand genomes in a hunt for clues to the genetics of aging.
But for now, I had a different question: If there really are such things as longevity genes, why don’t we all have them? Why hadn’t evolution blessed all of us with these wondrous, cholesterol-improving, brain-protecting, slow-aging, life-extending genes?