Only as old as your genes: Ashkenazi ‘super-agers’ could hold key to long life
‘Aging as we know it shouldn’t happen,’ says Israeli researcher Nir Barzilai, whose new book studies 750 centenarians, finding that drugs may delay the onset of major diseases
BOSTON — As COVID-19 ravages the globe, it has disproportionately affected elderly populations. But even before the pandemic, advanced age was often associated — fairly or not — with increasing health problems. In his new book, Israeli-born researcher Dr. Nir Barzilai questions this perception.
Intrigued by an Ashkenazi Jewish population in New York whose members often lived healthy lives past age 90 or even 100, Barzilai has devoted much of his career to studying such advanced agers. He shares his findings in “Age Later: Health Span, Life Span, and the New Science of Longevity,” published earlier this summer.
A Haifa native, Barzilai is the director of the Institute for Aging Research at New York’s Albert Einstein College of Medicine. He has gleaned insight from a population sample that now totals almost 3,000, including about 750 centenarians and their children.
Consider the four Kahn siblings, whom Barzilai got to know during their golden years. All lived past the century mark, and two — Irving Kahn and Helen (Kahn) Reichert — lived to be 109. Age did not stop Irving Kahn from working as an investor — or from taking a taxi to his office at age 108. Similarly, age could not prevent Helen Reichert from enjoying a cigarette — and neither could the doctors whom she outlived.
In a phone interview with The Times of Israel, Barzilai said that while he agrees that death remains a certainty of life, he is convinced that “aging, the way it is, shouldn’t happen.”
“I want to tell a story about why I think that,” Barzilai said. Amending himself, he added, “not ‘I think,’ but the science behind it.”
“People age at different rates,” he explained. “[Some] look 10 years younger, some 10 years older. There is a biological age. If you’re aging relatively quickly, you start accumulating diseases after the decade after [age] 60.”
These include the so-called “Big Four” of disease: diabetes, heart disease, cancer and Alzheimer’s. But not so for the Ashkenazi super-agers in his population sample.
“The first thing we learned is the most important,” Barzilai said. “It’s not that they get sick. Everybody gets sick.”
Yet, he said, the centenarians he studies live healthy lives 20 to 30 years longer than others born around the same time period.
“[At the end] of their life, they die rapidly, quickly, without disease [for their] last five to eight years like us,” Barzilai said, noting that when diseases finally do come, they last only “for a few weeks.” He calls this “a huge longevity dividend” that could potentially yield knowledge of how to “slow aging” and make “a lot of the need for hospice and medical care for disease go away.”
The book’s publication could not be postponed to include more about the coronavirus. Yet, Barzilai said, “COVID is exactly what I was talking about” — a pandemic that is affecting the “biologically old.”
“[It] is not the diseases themselves, it is the aging which makes you susceptible — in this case, to viral infection,” as well as “the ability of the body to sustain [itself] through a difficult disease, to survive a difficult disease,” Barzilai said.
Comparing the coronavirus situation to a war, Barzilai said, “You want to fight the virus… to do immunization. But in wars, you also defend the population and the soldiers too. We have to fortify the older adults. That’s what my book is about.”
Who are advanced agers?
Before COVID-19, Barzilai was speaking quite a bit about advanced agers — including at a TEDx Beacon Street talk at Boston University Medical School in January attended by The Times of Israel. He subsequently was interviewed in a Fox News podcast by former speaker of the House Newt Gingrich. Throughout, he was anticipating the release of his first book for a mass audience — “intelligent laypeople,” he said.
“The science is very, very simple, and whenever I felt there was a need for more science to be explained, there’s a chart or something so you can read what it means,” Barzilai said, adding that other features include “stories on centenarians, stories on biotech, drug development, about the future.”
There are also glimpses into Barzilai’s own life. A Technion graduate who completed his residency at Hadassah Medical Center, Barzilai rose to the position of chief instructor of medics in the IDF. His army service included a deployment to a refugee camp in war-torn Cambodia.
Subsequently, he studied medicine in the United States, at Yale and Cornell universities, before joining the faculty at Albert Einstein College of Medicine, where he holds the Ingeborg and Ira Leon Rennert Chair in Aging Research.
Barzilai’s own family includes his super-ager uncle Irving, a 98-year-old Holocaust survivor of multiple concentration camps. After World War II, Irving moved to Czechoslovakia, only to flee during the 1968 Prague Spring uprising. More recently, following a move to Houston, he lost his house to a hurricane four years ago but rebuilt it.
What’s next, bring it on, nothing’s going to kill me
Throughout, Barzilai said, his uncle approaches life with the same philosophy: “He asks himself what’s next, bring it on, nothing’s going to kill me.”
The Kahn siblings showed similar resiliency. Irving Kahn was described as the “Oldest Active Wall Street Investor” in his 2015 New York Times obituary. Eventually managing $1 billion in assets, he took a taxi to work as recently as the year before his death.
Each day, he read two financial newspapers, which Barzilai sees as reflecting an important issue as people age.
“The point is to activate the mind,” Barzilai said. “Maybe you can have an opportunity to do it because you have the genes to do it — not because you do it to keep your mind.” However, he said, “I think both are true to some extent.”
Barzilai characterizes the centenarians he has interacted with as generally “positive thinking, grateful, thankful, extroverts.”
Yet he said it is a mistake to assume these qualities are lifelong. He notes that significant changes may occur with age, from losing one’s spouse to moving into assisted living. And, he said, science has disproved the belief that personality remains constant after age 70.
Healthy habits only get you so far
Some centenarians follow habits that seem counterintuitive. Kahn’s sister Helen (Kahn) Reichert had a penchant for cigarettes, chocolate and Budweiser, as described in her 2011 NPR obituary — which noted that she outlived multiple physicians who advised her not to smoke.
Barzilai noted a misperception that centenarians owe their longevity to healthy habits.
“The answer is no,” he said. “They are very similar to the bad habits of the population.” However, he added, centenarians have “genes protecting them against the bad habits.”
For the general population, Barzilai said, exercising, eating right, and avoiding alcohol and tobacco are not ends unto themselves. Rather, he said, most people need to adopt a healthy lifestyle because “we are unlikely to have the genes that protect life against all these bad habits.”
Asked about the role of genetics in advanced aging, Barzilai said that the genetics is “strong” in centenarians but added that this wasn’t the only factor in living long.
Barzilai cites an example from his family history. His father and grandfather both suffered heart attacks at age 68. His grandfather’s was fatal, whereas his father survived, underwent triple bypass surgery and lived to age 84.
“You can see the genetics are similar,” Barzilai said. “My father had an interaction with the environment that was not available to my grandfather.”
“It’s very complicated to give numbers about how much is genetic,” he said. “It’s almost impossible to give a number. The point here is that if we can find all the genetics, we could protect against the environment, no matter what the number is.”
And, Barzilai said, “we are finding the longevity gene.”
He said that in studying advanced agers, he is finding “what in their genetics allows them to get to be 100,” with two findings already translated into drugs.
“It’s an impact we have on drug development from these Jewish centenarians,” he said.
In recent years, Barzilai has become intrigued by a drug called metformin that he is examining for possible protective effects against age-related disease. It is currently used to treat Type 2 diabetes. More recently, it has been tried against COVID-19. Earlier this year, a paper published in China reported less mortality among diabetic COVID-19 patients taking metformin than among those not taking metformin.
Barzilai cited past human studies in which participants using metformin had “less of the major diseases of aging,” with results being detected through either “clinical or observational” means.
“For me, metformin is a tool to show the FDA that aging can be prevented,” Barzilai said. “By targeting aging, we can prevent age-related disease.”
By targeting aging, we can prevent age-related disease
According to Barzilai, metformin can help realize the maximal lifespan for the human species, which he said is 115 years old.
“If we can reproduce metformin for aging, and if pharma develops more and better drugs and combinations of drugs, we can start making better progress,” Barzilai said.
COVID-19 has put Barzilai’s study on hold. He was in pre-study mode six months ago when the pandemic hit. He has yet to recruit his first participant.
“We will probably have to wait until it’s safe again to get patients to the study,” Barzilai said. “We would have been recruiting now, but cannot.”
Yet looking long-term, he is optimistic about what lies ahead for aging research.
“Now biotech is involved in this,” he said. “It’s why pharmaceuticals are going to be interested, why the future looks better. We can extend our health span and enjoy a better end of life, a better quality of life.”
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