A centenarian club

When Russell Snell and his colleagues at the University of Auckland, New Zealand, were recently designing a study to test a candidate Alzheimer's gene, they ran up against a roadblock: How to put together a control group? "It's a problem," says Snell. "How do you identify a person who is not going to develop Alzheimer's?"

The obvious answer was to find a group of healthy people who had passed the usual age of onset of the disease. "If you reach 95 or 100, or more, and you don't have Alzheimer's then you probably won't be getting it," he says. But gathering a sizeable cohort of centenarians and near-centenarians is no easy matter, certainly not in New Zealand, with a population of just 4.16 million. So Snell took to the literature, searching for other groups who had a cohort he might borrow.

He found the perfect sample in May 2005, when a paper in Proceedings of the National Academy of Science caught his eye (102:7906-9, 2005). It came from the lab of Stefan Schreiber and his group at University Hospital Schleswig-Holstein in Kiel, Germany, who had been investigating possible genes associated with longevity. Quickly reading through the report, Snell realized he'd found a centenarian gold mine. Schreiber's group had gathered a sample of more than 1,000 unrelated people between the ages of 95 and 109, with 373 of them topping 100 years. "There are some similar groups of centenarians, but not many," Snell says, "and this one, I think, is very special. The German population is very stable, and there isn't a lot of population admixture involving different ethnicities."

Schreiber agrees that this is one of the most valuable things about the German cohort. "Germany is one of the few countries without much ethnic admixture, which makes it much easier to adjust the control groups," he says. "Also recent admixtures of Caucasians or excessive geographical mobility, as we see in the US, can be a serious problem for such studies where the controls come from a birth cohort three decades later. That is clearly not the case for Germany."

Finding centenarians and nonagenarians for the cohort is actually fairly routine, Schreiber explains. The main sources the group used were Germany's population registries which list all inhabitants using Germany's National biobank project, Popgen. One year, they were also able to reach some centenarians through letters the German President sends out to congratulate people who reach 100.

Once the scientists have identified candidates from those two sources, they send out a letter asking for permission to send a questionnaire and a blood sampling kit. They also suggest that participants visit their general practitioner to have blood taken and to obtain help with filling out the questionnaire.

To qualify for inclusion, the participants have to be healthy, active, mentally fit, and able to answer a routine health-history questionnaire. It turns out, this isn't much of a problem. One of the fascinating things about the cohort is that the average centenarian seems to have a better quality of life than an average 80-year-old. "It seems that if you make it that far, you make it in decent health," Schreiber says. "A typical 100-year-old in our cohort still goes out and does the shopping, but a typical 80-year-old is often quite restricted in his or her ability to partake in daily life."

Meanwhile, the size and ethnic homogeneity of the cohort has attracted the attention of quite a few other research groups who want access for their own research, Schreiber admits. Not everyone is accommodated, however. "We have to limit it to research that is covered by the informed consent, and that means into questions addressing causes of death and, of course, longevity research," he says.

Longevity genes will remain the Kiel group's main interest. They've just completed a survey of all the potential leads coming from animal models, with mostly negative results. Next they want to embark on genome association and linkage studies. "We're confident that we will be successful," Schreiber says. "Look for results in about two years."