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.