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AGING Searching for the Secrets Of the Super Old More and more people are living past 110. Can they show us all how to age gracefully?

They were born when the years still started Perls of Boston University with “18.” They survived global traumas such School of Medicine, head as World War I, World War II, and the Great of the New England Cen- Depression. They didn’t succumb to pan- tenarian Study and its new demic flu, polio, AIDS, Alzheimer’s disease, National Institutes of or clogged arteries. , or Health–funded spinoff, the people who’ve survived to at least age 110, are New England Supercente- champions. narian Study. Researchers suspect that some Living to 100 is unlikely enough. Accord- of the oldsters included in the tally had already he requires three types of verification: proof ing to one estimate, about seven in 1000 peo- died and that others—or their relatives—were of birth, preferably a birth certificate; proof ple reach the century milestone. And at that lying about their ages. Drawing on Medicare of death, if the person is no longer alive; and age, the odds of surviving even one more year enrollment figures, two U.S. government “continuity” documentation, such as a dri- are only 50–50, says James Vaupel, director of actuaries put the number of supercentenarians ver’s license or marriage certificate, that the Max Planck Institute for Demographic in the year 2000 at a mere 105. And in 2002, shows that the putative is

Research in Rostock, . Making it 139 people claiming to be at least 110 were the person listed in the birth record. If candi- on February 5, 2010 from 100 to 110 “is like tossing heads 10 receiving Social Security payments. dates or their families can’t provide corrobo- times in a row.” “Claiming” is a key word. A crucial part ration, Young sleuths through census rolls, Researchers are keen to investigate these of studying supercentenarians is proving that school and military records, genealogies, 19th century holdovers. “If we want to better they were or are their stated age. No bio- and other types of paperwork. understand the determinants of longevity, we chemical test or medical exam can peg Using these methods, an organization have to look at the oldest old,” says biodemog- how old somebody is. So researchers often called the Research Group ver- rapher Jean-Marie Robine of INSERM’s turn to Robert Young of Atlanta, Georgia, a ifies the ages of living supercentenarians demography institute in Montpellier, . self-taught documents guru who confirms and posts a list online (www.grg.org). Young With Vaupel, he has recently compiled a the ages of the world’s oldest people for is senior claims examiner for the group, www.sciencemag.org demographic database of verified supercente- . Young comes which is headed by L. Stephen Coles of the narians from the industrialized countries. across like a veteran insurance adjuster who’s University of California, Los Angeles, an Two other projects, led by researchers on seen all the scams. To weed out pretenders, ob-gyn and computer scientist by training. the opposite coasts of the , As of last week, the roster included 10 men hope to pin down the traits of these survivors and 68 women from 12 countries, ranging by surveying their genomes for longevity- up to 115 years old. For reasons that remain

promoting DNA sequences and by autopsying murky, most supercentenarians are women. Downloaded from them when they finally die. Ultimately, work Moreover, of the oldest people ever docu- on supercentenarians could uncover “a unique mented, the majority have been women, [genetic] variation that explains their longevity including the record-holder Jeanne Louise that can be the subject of drug development,” Calment of France, who died in 1997 at the says molecular geneticist Nir Barzilai of age of 122. Albert Einstein College of Medicine in New To obtain a more complete count of York City. Such a discovery might not stretch supercentenarians for demographic analyses, human life span, but it could make our final Vaupel, Robine, and colleagues have dug years less grueling, suggests Barzilai. into national archives, including the records Yet studying supercentenarians is no easy of the U.S. Social Security Administration, to task. Finding these one-in-a-million people compile lists of candidates in 15 industrial- is hard enough, and validating their ages can ized countries. A team of age checkers then require that researchers become detectives or vetted each case. In all, the new International hire ones. Database on Longevity caches information on nearly 1000 supercentenarians from Come on, how old are you really? the past 50 years, although not every coun- Figures on the number of supercentenarians try’s records span this entire range. The are shaky. The 2000 U.S. census claimed a researchers plan to publish a monograph on total of 1400 living in the country. That num- Cutting for clues. L. Stephen Coles leads a group that has the database later this year.

ber is much too high, says geriatrician Thomas performed most of the autopsies on supercentenarians. But that still won’t be the final word. A OF L. S. COLES (BOTTOM) COURTESY R. YOUNG/NEW ENGLAND SUPERCENTENARIAN STUDY; OF GUZMAN FAMILY; CREDITS: (TOP LEFT TO RIGHT) COURTESY

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Turn of the century. The world’s oldest living person pens in the pipes of an old house happens in rationale is that the hormone’s blood levels is 115-year-old Edna Parker (right). Daniel Guzman your blood vessels,” says Coles. normally dwindle as we age. But Perls has (left), reached 111 before dying earlier this year. Perls and colleagues have also shown that blasted this off-label use of the hormone—it’s extreme survival runs in supercentenarians’ only approved for children with stunted lack of good records in developing nations families. Repeating an analysis they did earlier growth and adults with pituitary tumors or means that researchers still know little about for , the researchers last year ana- other rare conditions—as not only unproven the numbers of supercentenarians world- lyzed life spans of the siblings and parents of and potentially unsafe but also illegal in the wide, says demographer Bertrand Desjardins supercentenarians from the United States. The United States. of the University of Montreal in : “It’s team compared the relatives’ longevity with Working quietly outside that fray, Vaupel anyone’s guess how many supercentenarians that of people born in the same year. Brothers and colleagues plan to use their new database are living in China.” of supers gained about 12 to 14 years over their to answer a question that’s been nagging contemporaries, whereas sis- How to grow old in style ters outlasted their counter- Scientists have gotten a few hints about what parts by about 8 to 10 years. A keeps centenarians alive for so long—genes family connection doesn’t associated with a beneficial lipid profile, mean that only genes are for example (Science, 17 October 2003, responsible for supercentenari- p. 373)—but they’re just beginning their ans’ great age, Perls cautions. search for the sources of supercentenarian Everything from diet to exer- longevity. Two years ago, Perls and col- cise habits can also run in fam- leagues published the first health survey on ilies—the analysis can’t distin- these so-called supers, reporting on 32 peo- guish between genetic and ple between the ages of 110 and 119. “I think environmental factors. it’s incredible how well off they are,” says But Perls’s current work

Perls. Although almost half of the supers had might. He and his colleagues on February 5, 2010 osteoporosis and almost 90% had cataracts, have collected blood sam- 41% of them either lived on their own or ples from 130 authenticated required only minimal help with tasks such supercentenarians and have as preparing food, dressing, and bathing. sequenced DNA from 100 of Cardiovascular disease, the leading killer in them. As early as this fall, developed countries, was rare among super- the team could be ready to centenarians—only 6% had suffered heart submit a paper on gene vari- attacks and 13% reported strokes. Diabetes ants that might be stretching and Parkinson’s disease were also uncom- supercentenarians’ lives, he www.sciencemag.org mon in the group, striking only 3% of the says. Moreover, because the Saved by a SNP? Tom Perls (right) and colleagues are scanning DNA subjects each. Like centenarians, supercente- research team also has data on from people like 110-year-old Mary Marques for longevity clues. narians seem to be good at putting off the day the supers’ past health and when they become disabled, says Perls. lifestyles, it might be able to statistically tease demographers and actuaries: Do the odds of The superseniors deviate from the norm apart environmental and genetic influences dying in a given year, which rise relentlessly not just in how long they live but in how they on the oldsters’ life spans. for most of adult life, taper off in the most sen-

die, says Coles, who arranges autopsies of the The Supercentenarian Research Founda- ior seniors? Demographers want to determine Downloaded from oldest old as part of his work with the recently tion has similar ambitions. In addition to the whether the death rate stabilizes so they can established Supercentenarian Research Foun- autopsies this nonprofit group of doctors and test their models of mortality, whereas actuar- dation. Only nine supercentenarians have researchers has conducted, Coles and his col- ies need the answer to help governments undergone postmortems—Calment, for leagues have obtained a few blood samples refine budgets for health care and pensions. If example, never agreed to one—and Coles and and plan to start collecting more next year. mortality does peak or even begin to decline in colleagues have performed six of these proce- However, the effort, which is operating on very , it could mean that people who dures, including one earlier this year in Cali, donations, won’t have enough money to live past 110 really are super, stronger than the Colombia, on a man who died at age 111. sequence DNA from the samples. They will rest of us, Vaupel says. Coles argues, based on these autopsies, go into the freezer, but Coles says the shrink- If centenarians are any guide, researchers that supers aren’t perishing from the typical ing costs of sequencing technology should will find that supercentenarians have varying scourges of old age, such as cancer, heart dis- soon make reading the DNA affordable. backgrounds, lifestyles, and genetic profiles. ease, stroke, and Alzheimer’s disease. What The two projects will be sharing Young’s But as Robine notes, they share one factor: kills most of them, he says, is a condition, age-checking services but nothing else. Perls luck. Calment provides a prime example. She extremely rare among younger people, called says he declined to collaborate with Coles’s outlived her husband, daughter, and grandson. senile cardiac TTR amyloidosis. TTR is a pro- group in part because some of its members are They died from non-aging-related causes— tein that cradles the thyroid hormone thyrox- involved in so-called antiaging medicine, the husband from food poisoning, the daugh- ine and whisks it around the body. In TTR whose practitioners claim to be able to allevi- ter from pneumonia, and the grandson in a car amyloidosis, the protein amasses in and clogs ate time’s ravages with treatments such as accident. So if you hope to reach the big 110, blood vessels, forcing the heart to work harder injections of human growth hormone (HGH) keep a rabbit’s foot handy.

CREDIT: R. YOUNG/NEW ENGLAND SUPERCENTENARIAN STUDY CREDIT: and eventually fail. “The same thing that hap- (Science, 8 February 2002, p. 1032). The –MITCH LESLIE

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