February 22, 2020

DNA May Unlock Secrets of ‘SuperAgers’

Editor’s Note: Irving Kahn died at the age of 109.

It helps that Irving Kahn 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 8 p.m., gets up at 7 a.m., takes vitamins because his attendants tell him to. (However, he drew the line at Lipitor, a statin that reduces cholesterol, 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 never has had a life-threatening disease, who takes no cholesterol- or blood pressure-lowering 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.) Here, he cuts me off.

A man who at 105 never has had a life-threatening disease, who takes no cholesterol- or blood pressure-lowering medications and can give himself a clean shave each morning, invites certain questions.

He is not interested in his longevity.

But scientists are. A boom in centenarians is just around the demographic bend.

The National Institute on Aging predicts 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. Kahn agreed to have his blood drawn and answer questions for the granddaddy of these studies, the Longevity Genes Project at Albert Einstein College of Medicine in the Bronx.

The project seeks to determine whether people who live healthily into their 10th or 11th decade have something in common. If so, can it be made available to everyone else?

What have the researchers learned? Not what Kahn 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,” Sophie says.

“Oy vey,” Esther says.

“Oy veyizmir,” Sadie says.

“I thought we weren’t going to talk about our children,” Mildred says.

Early in the 20th century, 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).

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 geriatric-related websites. Four years later, upon turning 100, Irving rang the bell at the New York Stock Exchange. (Like her brother Irving, Helen died at 109.)

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 540 people older than 95. Like the Kahns, all 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. 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. (Although 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 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 did, 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 was 5 foot 2) may reflect the influence of a protective factor seen throughout nature: Ponies live longer than horses.

This story originated at nymag.com.