What Can the DNA of Ashkenazi Jews Tell Us About Living Longer? — New York Magazine

What Do a Bunch of Old Jews Know About Living Forever?

(Photo: Christopher Lane)

“Don’t be sad,” says Finklestein on his deathbed. “I’ve had 80 good years.”
“But you’re 98!” says his wife.
“I know.”

Except for the occasional doctor’s appointment or bad cold, Irving Kahn hasn’t skipped a day of work in more years than he can remember. And he can remember plenty of them: He’s 105.

That record is vexing to his youngest son, Thomas Graham Kahn, who though 69 and president of Kahn Brothers, their brokerage and money-management firm, is still called Tommy. (Irving is chairman.) How can he take a vacation if his father won’t?

Instead, Tommy threatens to dock his dad for his short workday, which begins around ten and ends by three and often includes a nice bowl of soup. “It’s not like we have so many employees we can afford to have him shluf off,” Tommy says.

Tommy runs the business, which has about $700 million under management. But even though Irving, with his very short stature and very large glasses, looks a bit like a horned owl peering up from his desk—a desk that features both a computer and grip bars—he is no figurehead. His is still the corner office, 22 floors above Madison Avenue. (During the blackout of 2003, he walked down.) He gives or withholds the papal blessing on investment policy and reviews every transaction undertaken by the firm’s youngsters on behalf of clients.

The world’s oldest stockbroker, he first went to work on Wall Street in 1928. “This was before the Depression,” he says, then specifies which depression, as if I might confuse it with the one in the 1890s. Both are real to him; through a chain of memory leading back to his grandparents, Eastern European Jews who settled on the Lower East Side shortly before that earlier upheaval, he can almost touch the Civil War.

More directly, he can touch the technological revolutions that followed. He describes his father’s good fortune in getting into the lighting-fixture business in the years after “Mr. Edison opened his downtown office”—the one that brought electric power to Manhattan in 1882. He remembers with perfect clarity building a crystal radio in his bedroom around 1920 and amazing his mother, who thought music came only from Victrolas, with the music he “caught for free.”

When you’re 53, as I am, and believe yourself to be on the wrong side of life’s unknowable midpoint, a conversation with someone who will soon be twice your age, and who furthermore has retained all his marbles, can be disorienting. For one thing, it has the effect of collapsing a century into a pancake. Czar Nicholas II and Barack Obama, gaslight and computer glow, grandmothers and grandchildren: All are contemporaries, all in sharp focus.

The indiscriminate urgency of memory is disorienting for Irving as well. “I’d rather not know who I was and who I knew and what I did,” he says. “It uses up space I need for today.”

By “today,” incredibly, he also means the future. All conversations with Irving eventually wobble back to his favorite ruts, such as how new technology might affect the viability of companies he follows. “I don’t worry about dying,” he says, assuming it will happen in his sleep. Instead he worries about staying mentally agile, which is why he reads three newspapers daily and watches all the C-Spans. “I know people collect postage stamps, but that’s just one thing. It’s about having multiple interests.”

He does not say multiple attachments; his own upbringing—his mother ran a shirtwaist business out of the home—suggested the value of independence and keeping an eye on the horizon. Newness served his family well: “A new country, a new language, a new public school, a new college.” At his home a mile up Madison—until he was 102 he took the bus—he has, he says proudly, “thousands of books, not one fiction. Mostly I’m interested in what’s on the edges: solar energy, sending vehicles beyond the moon.”

His belief in a personal future that will repay this curiosity—a future I can hardly imagine for myself without worries of illness and decrepitude—is what’s most disorienting about Irving Kahn. You’d think that as he got older, then even older, and then bizarrely old, he’d have had ever more opportunities to despair. And, true, his eyesight and “earsight” aren’t what they were. He can’t walk much on his own anymore. He despises these limitations but ignores or finds ways to outwit them. Loss as well. His wife’s death, in 1996, was a huge blow, Tommy reports, but Irving “put his foot down a little more on the pedal, if that was possible.” When macular degeneration recently made reading difficult, he learned to enlarge the font on what he calls his Gimble.

It helps that he is wealthy enough to have full-time attendants. Also, perhaps, that he has always been a “low liver,” without flamboyant tastes, as his brown, pointy-collared shirt and brown patterned tie attest. He goes to bed at eight, gets up at seven, takes vitamins because his attendants tell him to. (He drew the line at Lipitor, though, when a doctor suggested it a few years back.) He wastes few gestures; as we speak, his hands remain elegantly folded on his desk.

Still, a man who at 105—he’ll be 106 on December 19—has never had a life-threatening disease, who takes no cholesterol or blood-pressure medications and can give himself a clean shave each morning (not to mention a “serious sponge bath with vigorous rubbing all around”), invites certain questions. Is there something about his habits that predisposed a long and healthy life? (He smoked for years.) Is there something about his attitude? (He thinks maybe.) Is there something about his genes? (He thinks not.) And here he cuts me off. He’s not interested in his longevity.

But scientists are. A boom in centenarians is just around the demographic bend; the National Institute on Aging predicts that their number will grow from the 37,000 counted in 1990 to as many as 4.2 million by 2050. Pharmaceutical companies and the National Institutes of Health are throwing money into longevity research. Major medical centers have built programs to satisfy the demand for data and, eventually, drugs. Irving himself agreed to have his blood taken and answer questions for the granddaddy of these studies, the Longevity Genes Project at Albert Einstein College of Medicine in the Bronx, which seeks to determine whether people who live healthily into their tenth or eleventh decade have something in common—and if so, whether it can be made available to everyone else.

What have the researchers learned? Not what Irving wanted to know, which was only whether those who live longer have higher earning power. For the rest, like how he got involved in the Einstein study, he says, “You’ll have to ask my sister.”

His older sister.

“Oy,” says Sophie.
“Oy vey,” says Esther.
“Oy veyizmir,” says Sadie.
“I thought we weren’t going to talk about our children,” says Mildred.

Between 1901 and 1910, Saul and Mamie Kahn—the electric-fixture salesman and his clever wife—had four children: two girls (Helen and Leonore), then two boys (Irving and Peter). By 2001, when Helen turned 100, they were thought to be the oldest quartet of siblings in the world. Helen’s sassy tongue and taste for Budweiser made her a minor celebrity on old-age websites; four years later, upon turning 100 himself, Irving rang the bell at the New York Stock Exchange.

But the family’s DNA may be even more celebrated. All four have participated in Einstein’s longevity research, begun by Dr. Nir Barzilai in 1998. For these studies, Barzilai has assembled a cohort of some 540 people over the age of 95 who, like the Kahns, reached that milestone having never experienced the so-called big four: cardiovascular disease, cancer, diabetes, and cognitive decline. He theorized that these “SuperAgers,” as he calls them, must have something that protects them from all four conditions. Otherwise, when they didn’t have a heart attack, say, at 78, they’d have succumbed quickly to the next thing on their body’s inscrutable list. So instead of looking, as most genetic studies do, for pieces of DNA that correlate with the likelihood of getting diseases, Barzilai looked for the opposite: genes that correlate with the likelihood of not getting them—and thus with longevity.

The top correlate for longevity is one that requires no blood test to discover: having a SuperAger in your family already. (Though Mamie died at 64, Saul lived to 88, exceptionally long for a man born in 1876.) But the results at the DNA level are nearly as strong. Barzilai has so far identified, or corroborated, at least seven associative markers. The most significant is the Cholesterol Ester Transfer Protein gene, or CETP, which in one unusual form correlates with slower memory decline, lower risk for dementia, and strongly increased protection against heart disease. (Among other things, it increases the amount and size of “good” cholesterol.) Only about 9 percent of control subjects have two copies (one from each parent) of the protective form of CETP, while 24 percent of the centenarians do, including all four Kahn siblings.

Other markers found more frequently among the SuperAgers include a variant of the APOE gene that protects against atherosclerosis and Alzheimer’s, a variant of the FOXO3A gene that protects against tumor formation and leukemia, and a variant of the APOC3 gene that protects against cardiovascular disease and diabetes. (This variant alone has been associated with an average life extension of four years.) Having long telomeres—regions at the ends of chromosomes that shorten as you age—is another kind of marker, acting as an instant-read longevity thermometer. There’s evidence, as well, that small stature among the SuperAgers (Irving is now about five foot two) may reflect the influence of a protective factor seen throughout nature; ponies live longer than horses.

Suggestive though they are, these findings so far lack the real-world application that can turn even the most questionable longevity fads, like Resveratrol, into worldwide sensations. After all, as Tommy Kahn puts it, would you really want to know if you have a predisposition for your penis falling off unless there were “some kind of splint” you could get to repair it? (Tommy, a widower, recently remarried.)

But the Einstein project is fascinating for a major reason beyond its science: Its main test group consists entirely of Ashkenazim—that is, Jews who descend, as more than 80 percent of American Jews do, from communities in the Pale of Settlement of Eastern Europe. In longevity news, the spotlight frequently passes from one group to another: Georgian yogurt eaters, Japanese pensioners, the Pennsylvania Dutch. But 540 Jews in a New York–based study of extreme old age is too delicious. The mind cramps with the possibility of jokes.

Barzilai acknowledges as much, telling me first off that most of the original intakes were done by a Gentile nurse named William Greiner. After Greiner visited the participants in their homes, interviewing them and taking their blood, Barzilai would get calls saying that the young man was very nice, but why didn’t he touch the cake they’d prepared?

Mostly gray at 56, Barzilai, Israeli by birth, is a puffball of excitability: twinkling, gesturing, capable of persuading anyone to do anything. Well, almost anyone. His mother, a Holocaust survivor born in what is now Ukraine, refused to let him test her blood. “For her, the genetic studies had already been done,” Barzilai recalls. “And she didn’t enjoy it the first time.”

He laughs, but the twinning of darkness and lightness in his life’s work is no accident. Longevity is the flip side of mortality, as Jews who survived the twentieth century do not need reminding. When a centenarian says she’s Ashkenazic, he takes her word for it: “Do you think there would be impostors?” And when he goes to synagogues to solicit volunteers, he makes this argument: “Yes, we had a miserable history, okay, let’s get over that, we ended up not in such a bad place. And if we’re able to give back, to find genes associated with longevity, it’s really something we have to do. I’m not choosing Ashkenazim because of only a technical point, but also tikkun olam“—the rabbinic injunction to repair the world.

As it turns out, the miserable history is inseparable from the technical point. Barzilai centered his studies on Ashkenazim not because they live longer or produce more centenarians than other ethnic groups. They don’t. It’s that their unusual development as a homogeneous community makes them easier to study at the level of DNA. Genetic research done by Barzilai’s Einstein colleague Gil Atzmon suggests that Ashkenazim branched off from other Jews around the time of the destruction of the First Temple, 2,500 years ago. They flourished during the Roman Empire but then went through a “severe bottleneck” as they dispersed, reducing a population of several million to just 400 families who left Northern Italy around the year 1000 for Central and eventually Eastern Europe. Though their numbers increased dramatically once there, to some 18 million before the Holocaust, studies suggest that 40 percent of today’s Ashkenazim descend from just four Jewish mothers. How proud those mothers would be to know that the reason their mishpocheh has remained far more genetically alike than a random population—Barzilai says by a factor of at least 30—is that until recently their sons almost never married outside the clan.

That likeness means that small genetic differences—as small as one “letter” of DNA code—are more easily spotted on Ashkenazi genes than on those of, say, Presbyterians. Icelanders are good, too: They are all descendants, Barzilai says, of five Viking men and four Irish women. But they are a tiny population, with proportionately fewer centenarians, and aren’t so easy to find in New York. Ashkenazim are plentiful. And because they are also fairly similar in their educational and economic status, some of the variables that can muddy the picture are already controlled.

Others are controlled more explicitly. An Einstein study published in August asked whether the SuperAgers, over the course of their lives, had better health habits than the general population.

The answer was no; their habits were, if anything, worse. They smoked as much or more than others and were no better about diet or exercise. Tommy Kahn described his father’s lifelong eating habits as “lamb chops one night, steak the next.” Exercise was sporadic and mild. “Healthy living can get you past 80,” says Barzilai, “but not to 100.” Something else is at play. When asked what they themselves thought it might be, the participants offered such explanations as genes, luck, and family history. God, says Barzilai, finished last.

Read the Rest of the article here: http://nymag.com/news/features/ashkenazi-jews-2011-11/

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