To Measure Longevity, Common Sense Trumps Genetic Test

With several companies on the verge of mass-marketing genetic tests that claim to read aging’s cellular clock, some researchers say the science isn’t yet ready for prime-time use. The tests measure telomeres, or protein sheaths that prevent the tips of chromosomes from fraying. As time passes, they grow shorter, a process hastened by stress, environmental […]
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With several companies on the verge of mass-marketing genetic tests that claim to read aging's cellular clock, some researchers say the science isn't yet ready for prime-time use.

The tests measure telomeres, or protein sheaths that prevent the tips of chromosomes from fraying. As time passes, they grow shorter, a process hastened by stress, environmental insult and disease. If they get too short, cell breakdown follows. A large body of research links telomere deterioration to deteriorating health.

That makes telomeres an alluring target for quantifying the ravages of aging, which have proved surprisingly difficult to measure. But the clinical use of telomeres has yet to be determined.

"Aging is extremely complex. It's going to involve many behavioral and genetic factors," said Boston University gerontologist Thomas Perls, who runs the world's largest study of centenarian health. "It's going to be unwise to try and pin it down on one particular marker. There are going to be many different factors."

Telomere tests came to public notice this week after an article in The Independent described a test being developed by Life Length, a Madrid startup company. In the article, University of Texas Southwestern geneticist and Life Length consultant Jerry Shay extolled the test's potential.

>'When you're looking at a whole bunch of people, you conclude that shorter telomeres are bad. But that doesn't mean you can take an individual and tell them their risk.'

"Telomere length is actually a pretty good representation of your biological age," he said. "People might say 'If I know I'm going to die in 10 years, I'll spend all my money now.' Or, 'If I'm going to live for 40 more years I'll be more conservative in my lifestyle.'"

Shay's comments seemed to verge on touting Life Length's $700 test as a fairly precise predictor of longevity, something researchers generally agree isn't now possible. The company officially describes the test as a general measure of health. That description is in keeping with a $290 test offered by Houston's SpectraCell Laboratories and another in development by the California firm Telome Health.

The latter company was co-founded by Elizabeth Blackburn, one of three researchers who in 2009 shared a Nobel Prize for their work on telomeres. But whereas Life Length plans to offer its test directly to the general public, SpectraCell requires that tests be provided by physicians on behalf of their patients. That requirement that will be shared by Telome Health, who currently offer tests only to researchers.

"We do have a plan to address consumers through their physicians, but where we see the largest long-term value is with properly validated clinical studies in the area of case management with severe illnesses," said Telome Health chief scientific officer and co-founder Calvin Harley. According to Harley, telomere length can't predict longevity, but "there is a risk factor associated with having shorter telomeres. People should be able to utilize telomere length into their personal health management through their doctors."

Yet for Johns Hopkins University geneticist Carol Greider, who also shared that 2009 Nobel prize, such mainstream testing is premature.

Except for 1 percent people whose telomeres are spectacularly short, and are thus likely to have family histories of telomere-linked diseases like pulmonary fibrosis and bone marrow failure, "We don't know for any individual what this would mean," said Greider. "There are no clinical studies that tell us anything about the other 99 percent."

The science is indeed complicated, if not downright murky. Whereas tests in cell cultures, animals and those 1 percent of human outliers have established the importance of telomeres, population-level effects are hard to define. Some researchers still say the general link to longevity is "equivocal." Even when telomeres are linked to health, the results can be complicated.

"The question is, how much can you tell people right now? And with what confidence?" Greider said, calling attention to a 2005 Lancet study on telomeres, obesity and cigarette smoking in women (.pdf). On average, telomere length and age were linked in the study's 1,122 subjects -- but on a person-by-person basis, the numbers were widely scattered (see graph at right.)

"Look at someone who is 40 years old. Your telomere length can be at 5 kilobases or 9 kilobases," said Greider. "In an epidemiological study like this, when you're looking at a whole bunch of people, you conclude that shorter telomeres are bad. But that doesn't mean you can take an individual and tell them their risk."

For now, the best indicator of longevity and aging comes from not from telomeres or any other genetic measure, but a common-sense mix of family history and lifestyle, said Perls. He offers an online questionnaire for people interested in evaluating their health. (According to Perls, the service is non-commercial, with advertisements defraying server costs.)

"If people want a prediction, it's their health-related behaviors that are going to be by far the most important and powerful predictor," he said. "And they need to pay attention to that. You can't pick your parents, but you can pick whether you smoke, exercise and have a healthy diet. It's great to get markers, but it's much more powerful if predictions are based on something you can affect."

Image: Telomeres (illuminated with fluorescent tags) at the tips of chromosomes (NIH).

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