The science of ageing well


By Lori Aratani

Every year hundreds of people travel to Baltimore for an unusual purpose. They are not there to tour the city's aquarium or sample its fabled blue crabs. They are not in search of fame or money. Other than free lodging, they receive nothing in exchange for their visit, which entails a certain amount of discomfort.

No, these folks, some of whom have made this journey for decades, believe the trip is worth their time and expense because how they live - calculated according to everything from the strength of their grip to how many apples they consume in a month - may offer clues to how the rest of us might live better, longer, healthier lives.

These individuals - homemakers, pensioners, doctors and a myriad others - are participants in the Baltimore Longitudinal Study of Ageing (BLSA), the US's longest-running study of ageing.

Since 1958, a total of more than 1 400 volunteers have agreed to regularly undergo in-depth physicals and other screenings conducted by the study's physicians. The resulting data spans more than half a century and is a gold mine for researchers interested in the ageing process.

Because of the BLSA, scientists know that signs indicating that a person could be at risk for dementia and other cognitive diseases may appear 20 years before symptoms emerge. Findings that today are common knowledge (that exercise can help reduce high blood pressure, for example) can be traced back to BLSA's annual physicals and the data analysis done by the study's scientists.

Think of it as a vast historical record.

The BLSA is one of many projects being done by the National Institute on Ageing, but the study itself is a rarity. Few institutions will undertake such an extensive venture, largely because the commitment required from individuals is enormous, said the study's director, Luigi Ferrucci.

It's not just researchers who toil for years sifting through mountains of data. BLSA participants also are devoted to helping researchers fulfil the study's goals. One person has been enrolled for 47 years. The oldest participant is 102 and has made the required pilgrimage to Baltimore regularly for 38 years.

"Participants really, really love the study," said Ferrucci, a genial, grey-haired physician who first learned about the BLSA as a student in his native Italy. "They feel they are making a contribution to science, and they feel like ageing is such an important and under-studied issue, anything they can do to help, they want to do." Participants come from as far as Norway. Some even donate their bodies to the BLSA autopsy study.

"It's a chance to make a unique contribution to research on ageing," said Richard Sprott, one of the participants, "since this is the only research project of its kind in the world."

As understanding of ageing has changed, so have elements of the study. Researchers recently incorporated a new component into their research: Insights Into the Determinants of Exceptional Ageing and Longevity study (Ideal), an effort to uncover the secrets of those who age exceptionally well. Think 80-year-olds who ski and jog or 90-year-olds whose hearing and memory put a 30-year-old to shame. Ferrucci estimates only about 0.5 percent of the population has such abilities.

The lift doors slide open to reveal a tastefully decorated lobby. Soft music plays in the background. A huge bank of windows offers a soothing view of the Patapsco River. A smiling receptionist greets visitors warmly. For three days, the fifth floor of Harbour Hospital in Baltimore will serve as home base for the many participants who come for their physicals. Most will stay here at the hospital in comfortable, but not particularly plush rooms. Proximity is important because researchers want them to be available for the battery of tests they'll undergo over the next 48 to 72 hours.

Down the hall is a small kitchen stocked with fruit and pretzels. The atmosphere is soothing, the magazines plentiful, the staff friendly.

There is homework. Along with athletic shoes and casual clothing, participants are asked to bring with them a food diary that details everything they ate in the previous three days. Yes, some people have been know to temporarily clean up their diet, a tendency that is noted in the 20-minute introductory video sent to people before they arrive.

"Please report what you actually eat, not what you think you should be eating," it says.

This is no vacation. During their stay, participants will have a physical that goes well beyond sticking their tongues out and saying "ahh". They rarely will sit for more than 30 minutes before they are whisked away for another exam or stuck with another needle. Sprott, now in his 12th year in the study, confirms that the pace can be brutal.

Researchers take routine measures (temperature, blood pressure and weight) but participants also undergo more sophisticated tests. Echocardiograms help researchers examine hearts, and spirometry tests measure lung function. In addition to collecting blood and urine, researchers might also take samples of the participants' breath.

Even simple tests can provide valuable insight. Researchers will evaluate a participant's grip strength, which previous BLSA research has shown can predict whether someone might be at higher risk of complications after surgery or more likely to die prematurely.

A select few will undergo a procedure called cytapheresis, in which white blood cells are extracted from blood in a search for clues to how age might influence a person's immune system. In another test, participants' movements are tracked by sensors similar to those used in making computer-animated movies such as Toy Story.

The researchers do not offer treatment. They may, however, share information gleaned from the tests with participants, who can then discuss the findings with their regular physicians, Ferrucci said.

The researchers also evaluate changes in each person's memory and verbal ability, using memory tests and brain scans. Should a group of participants develop dementia, researchers can look back at those individuals' test results for commonalities.

So, what it is like to be a test subject?

Fascinating but not always fun, according to Sprott.

Most people mark another year with an extra candle on their birthday cake. But Sprott, 68, is reminded of his age when he slips up on one of the routine memory tests or when he is slightly more winded after a treadmill session he may have sailed through years earlier.

"It's a three-day validation that your body is going to hell," Sprott said with a chuckle. "And it reminds me every once in a while that I need to lose a little weight."

It's not the poking and prodding, the needles and the skin electrodes that Sprott dislikes. "The physical stuff doesn't bother (me)," he said. "We're all deteriorating."

Rather, it's the tests of memory.

"We hate the cognitive stuff," he said, going on to describe the test that he and his wife, who is also a participant, dread.

"The tester reads you a set of shopping lists, maybe 16 items," he recalled. "You have to reply with as many as you can remember. The first time you take this test, you discover a simple strategy for remembering: You sort the items into categories. But even though you take the same test every two years and you know the strategies, you get worse."

Sprott is well-versed in the science of ageing: For more than a decade, he directed the National Institute on Ageing's study on the biology of ageing. Since 1998, he has been executive director of the Ellison Medical Foundation, in Bethesda, Maryland, which funds basic biological and biomedical research on ageing.

"There is an incredible amount of misinformation out in the field," he said, adding that few programmes can match the longevity of the BLSA or the breadth of its data.

"My grandkids will benefit from this research," he added.

In addition to his wife, Sprott's 42-year-old daughter is also a BLSA participant.

The work done by BLSA scientists (more than 800 scientific papers) runs the gamut from the impact of ageing on major organs to its effect on personality, and it has become a standard reference on ageing.

Andrea Halpern, a professor of psychology and neuroscience at Bucknell University, has had students in her upper-level course on cognitive ageing review BLSA research. Already a "rich database" of information, she said, the research will continue to grow in importance as people live longer.

"The BLSA isn't perfect," said Alan Zonderman, senior investigator for the cognition section of the National Institute on Ageing. "There are limitations to it. But all of the limitations are overcome by the fact that we have all of these repeated measures on these people that no one else has."

When a participant falls ill, researchers can examine decades of records to find a cause.

"We can say, maybe it's not what's happening to them now, but what happened 20 years ago," said senior investigator Susan Resnick, who is principal investigator of the brain-imaging component of the BLSA.

"Probably the most frequent complaint people in their 70s make to their physicians is how bad their memory is," Zonderman said. "People worry about dementia in some ways more than they worry about getting cancer."

"A lot of our work focuses on early detection," he continued. "We're able to predict in some cases, not very accurately at this point, but with increasing accuracy... who is likely to get the disease, who is at the highest risk."

Zonderman was part of the team that found that changes in BLSA participants' visual memory may help predict future mental changes as well as signal the onset of diseases such as Alzheimer's.

Other BLSA studies have found that loss of some short-term visual memory is normal as people age, as is loss of some hearing.

BLSA researchers were able to disprove the long-held belief that people get crankier as they age. Using data collected from the study's participants, they found that personality traits don't generally change much after age 30; people who were cranky at 27 were likely to be cranky at 87.

Researchers also found that older people were better able to handle stress than their younger counterparts, who tended to cope by becoming hostile or retreating into fantasy worlds.

In another study, 50 BLSA men were given the equivalent of three martinis over the course of an hour to find out whether age influenced a person's ability to metabolise alcohol. It turns out the older participants were able to metabolise the alcohol just as well as their younger counterparts. However, older men did show greater impairment as a result of their consumption.

The possibilities that such data offers are endless. "This a treasure," Ferrucci said. "Who else is going to do a study that's going to last 50 years?"

Despite all those possibilities, there is one thing the BLSA can't do: stop people from getting old. But Ferrucci is confident the data gathered in 2009, like the research gathered during the first years of the study, will yield insights into how people can age gracefully.

"The definition of being old is changing; it's breaking apart," Ferrucci said. "People want to live well, no matter what their age is." - The Washington Post


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