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Discovering the secrets of long, healthy lives

March 1, 2009
Pair of older women

Like many retirees, Jim likes to keep busy. He tends his garden, putters around the house, and volunteers at the local hospital. A widower, he enjoys visits with his three daughters and four grandchildren. He became a great-grandfather in June.

It all sounds pretty routine—except that Jim is 98 years old and, despite an eye disease that forced him to give up driving last year, is pretty healthy overall. Even more remarkable is the fact that 7 of his 10 siblings are still alive, all of them in their 80s and 90s. “My kid sister is 80,” he notes.

The extreme longevity of Jim’s family and others like them interests scientists, who want to find out what makes them tick so well for so long. The Long Life Family Study (LLFS), sponsored by the NIA, aims to discover which genetic, environmental, and other factors keep the “oldest old” families relatively healthy.

“This is a groundbreaking study because it is the first and largest to examine both siblings and children of the very old,” says Winifred K. Rossi, deputy director of the NIA’s Division of Geriatrics and Clinical Gerontology. “We hope this will be a longitudinal study where we can study their families for many years.”

“There has been a lot of research on disease, but there’s more interest lately in health,” says Dr. Michael A. Province, a professor of biostatistics at the Washington University School of Medicine in St. Louis, which is gathering data from four study sites, three in the United States and one in Denmark. “There’s quite a bit of evidence about factors, particularly genetic factors, that allow people to be healthy and live a long life.”

Information about the common characteristics of families who live well into their 80s, 90s, and 100s could one day be used to guide lifestyle advice and medical treatments that help others live long, healthy lives. The number of Americans 85 and older rose from 100,000 in 1990 to 5.3 million in 2006—and is expected to near 21 million by 2050, according to the U.S. Census Bureau.

Recruitment challenges

Researchers involved in the 5-year LLFS hope to obtain data for 4,800 participants, including subjects, their siblings, and their children. They began recruiting in 2006 and, as of July 2008, had 2,400 participants, with 1 year of recruiting left to go. “The biggest recruiting challenge is finding participants and getting them to respond and getting them engaged,” Ms. Rossi says. “It’s a lengthy process.”

LLFS investigators are looking for families with a history of long life to participate in the study. Families that have at least two very old living siblings may be eligible and are encouraged to contact the study recruitment staff. At least one of the long-lived siblings must live within a few hours’ drive of the U.S. study sites—Boston University, the University of Pittsburgh in Pennsylvania, and Columbia University in New York City—though their siblings and children can live elsewhere.

Potential participants, culled from a database of Medicare participants, were contacted by letter. Study investigators have also advertised in local and national media and distributed fliers at senior centers, retirement communities, and other elder-friendly places to let people know about becoming part of study. The fourth study site, the University of Southern Denmark, recruited participants through Denmark’s church-run population registries.

Helen, 86, joined the study earlier this year after seeing a flier about it at a senior center near her home in a retirement community in Massachusetts. She then got three of her brothers and three of her sisters involved. (One of the 11 siblings is not participating; 3 others are deceased.)

“We thought it was interesting, and we thought we’d learn something,” Helen says. “We have a lot of things to offer,” adds her 88-year-old sister, Muriel, who describes herself as “quite a walker.” She hopes the study results will benefit future generations.

Potential participants are screened to make sure they meet the study criteria as relatively healthy older adults; those cognitively impaired or confined to a bed or wheelchair cannot participate. Finding healthy individuals at such advanced age is difficult, since the rate of frailty and illness is high among that age group. “These are exceptional families,” who make up only 1 to 2 percent of the population over age 85, Dr. Province says.

During a 2- to 3-hour interview, investigators ask participants about their personal and family health, including chronic diseases, medications, and smoking. They assess physical functioning with tests for grip strength, walking, and breathing. Finally, they obtain blood samples, which will be analyzed to find genetic characteristics shared by families as well as any genetic variants that set them apart from the general population.

The mystery of extreme longevity

Investigators are still recruiting participants and collecting data, so findings from the study are some years away. Previous research on centenarians and other very old people points to a familial link in extreme longevity, though LLFS researchers are also looking at nongenetic factors, including physical activity, social networks, and waist circumference.

“There’s something that keeps people robust,” Ms. Rossi says. “We suspect it will be some combination of genetics and environment.”

It’s not that very old people don’t get sick. They often do, but at later ages than the general population. Many people believe that the older a person gets, the sicker he or she becomes, notes Dr. Thomas Perls, of the Boston University School of Medicine and one of the LLFS principal investigators. But in fact, he says, research suggests that the older an individual gets, the healthier he or she has been.

Long-lived individuals’ siblings and children also tend to live longer and be healthier than their peers. One study found that middle-aged children of parents who lived to at least age 85 had a significantly lower risk of cardiovascular disease than children whose parents had died at younger ages. This risk-factor advantage persisted during 12 years of follow-up and was stronger in children of two parents who lived to 85 or more than in children with just one or no long-lived parent.

Is exceptional old age the result of rare genes? Healthy habits? Good luck? Some study participants credit their longevity to more subtle influences. Jim’s philosophy is to stay busy and be nice to people. Muriel observes, “The reason you can live a long time is you don’t complain about things.” That’s certainly food for thought about longevity. In a few years, the Long Life Family Study may reveal some of science’s secrets to a long, healthy life.

References

Individuals interested in participating in the Long Life Family Study are invited to call the study coordinating center toll-free at 877-362-2074. For more information about the study, go to https://longlifefamilystudy.wustl.edu.

Perls, T.T. The different paths to 100. Am J Clin Nutr. 2006 February. 83(2):484S-87S.

Terry, D.F., et al. Characteristics of Framingham offspring participants with long-lived parents. Arch Intern Med. 2007 March 12. 167(5):438-44.

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