2013年5月14日星期二

How long will you live?

Tomiko Kadonaga, who turned 100 on Jan. 8, will tell you she’s had an easy life. Others would say differently. Kadonaga, who was born in B.C. to Japanese-Canadian parents, was placed in an internment camp during the Second World War, housed with her husband, Saul, in buildings intended for livestock. “The stall where I was had a little blue card outside that said, ‘First Prize Cow,’ ” she says with a wry smile. “I thought, ‘At least I’m first prize.’ ” Her godmother offered Saul a job on a farm in Port Hope, Ont., and a way out; leaving all their possessions behind, they moved to the area in 1942, and had a daughter. Saul died of esophageal cancer in 1989.

Today, Kadonaga, who lives alone in a neatly kept townhouse in Toronto’s north end, is the picture of contentment. Her legs bother her a bit, she says (she gets around with a flowery purple cane), but otherwise she’s in good health. In Canada, average life expectancy is 81, yet more people than ever are living to be 100. In 2011, we had 5,825 centenarians, according to Statistics Canada, up from 3,795 10 years before. As life expectancy continues to rise, it could hit over 17,000 by 2031. Why some people outlive almost everyone else—and remain in good health, even into very old age—remains one of the grand questions of science. Researchers have credited everything from diet and exercise to genetics. A clue to the secret of Kadonaga’s longevity, one we’re only starting to understand, lies buried deep within her cells: the tiny bits of DNA that cap the ends of her chromosomes, called telomeres.

Telomeres shorten as we age, but the telomeres of centenarians are remarkably long, according to Gil Atzmon at the Albert Einstein College of Medicine in New York—more like those of people three decades younger, or even younger than that. Often compared to the plastic ends that keep shoelaces from fraying, telomeres prevent chromosomes from unravelling and fusing to each other. Each time a cell divides, some of the telomere is lost; when it becomes too short, the cell dies. Telomeres are protected by a powerful anti-aging enzyme, one produced by our own cells: it’s called telomerase, which rebuilds telomeres and protects them from wearing down, a discovery that won scientists Elizabeth Blackburn, Carol Greider and Jack Szostak the Nobel prize in 2009. Healthy people with longer telomeres seem to be at lower risk of age-related illness, such as heart disease, diabetes and cancer—the main diseases that stop us in our polished tiles.

A growing number of researchers say telomere length is a critically important indicator of how old we really are, and of how many healthy years we may have in front of us. A new industry is sprouting up around the science of longevity, offering telomere testing to the public—and Nobel laureate Blackburn is a notable part of it. Her company, Telome Health , is set to launch a telomere test later this year, joining a handful of others that already do. On May 15, Blackburn will be in Toronto to give a lecture sponsored by Executive Health Centre, a private clinic that offers telomere testing in Canada. Like a cholesterol or blood-pressure test, telomere testing could one day become standard in doctors’ offices.

And maybe in the future, we’ll be able to slow or reverse the effects of aging—the vision of researchers searching for ways to boost telomerase, a goal already achieved in lab mice. Some are already marketing so-called “telomerase activators” to a public hungry for ways to stop the clock, although no such drugs have been approved. With so many companies rushing to come on board, “there’s a lot of weird stuff going on out there,” cautions Jerry W. Shay of the University of Texas Southwestern Medical Center, an expert on cell biology and telomere length.

Even telomere testing isn’t without controversy. Greider, Blackburn’s former graduate student, insists that public testing is premature. Dr. Peter Lansdorp, another prominent expert on telomere biology, agrees. “It’s too early, and it’s not supported by scientific data,” he contends. But in an unpublished study presented in late 2012, Blackburn and her colleagues tracked 100,000 people (their average age was 63), and found that those with shorter-than-average telomeres had a 25 per cent greater risk of dying, from any cause, over three years. Telomere shortening is a dynamic process, and length can go up and down through life; there’s still a lot to learn, but “what happens to telomeres really does predict what happens to you later on,” says Blackburn, who’s based at the University of California, San Francisco (UCSF).

For those who’d like a glimpse into their longevity—a hint at true biological age—scientists say they can peer at the tiny caps on their chromosomes and, for better or worse, tell them what they see.

To scientists who study aging, a person’s birth date is increasingly irrelevant. “There’s an idea that we can do nothing about age,” says Felipe Sierra, director of the U.S. National Institute on Aging’s division of aging biology, which funds research into everything from stem cells to telomeres. “While that is true of your chronological age—you have a birth certificate, and that’s it—you can affect the rate of aging.” Ultimately, he says, “chronological age is not so important.” He calls telomere length a “good biomarker of aging,” but won’t comment on whether the public should be seeking out tests.

Scientists are still figuring out what speeds up telomere shortening. Chronic stress seems important. With UCSF psychologist Elissa Epel, Blackburn studied the telomeres of mothers of children with long-term illnesses. Compared to moms of healthy kids, they had shorter telomeres and less telomerase. “We repeated this with spouses who were caretakers of Alzheimer’s patients; it showed the same result.” Other studies have revealed that victims of domestic abuse, or those who suffer from untreated depression, also have shortened telomeres, putting them at greater risk of age-related disease. Shorter telomeres have been associated with cardiovascular disease, some types of cancer, diabetes, osteoperosis, dementia and other conditions.

Blackburn decided to transfer her technology out of the university, to cope with demand. “All sorts of people were wanting to find out about telomere length,” says Blackburn. “We had in our minds it would be interesting for people to know about their health status.”

Still, the “million-dollar question,” as Telome Health president Calvin Harley calls it, remains what can be done about short telomeres. Studies suggest lifestyle interventions—diet, exercise, meditation—could help slow down telomere shortening or boost telomerase activity, but it’s still early days. Harley insists that telomere testing is valuable. He compares it to a “check-engine light, evidence your cellular aging may be accelerated.” A Canadian, he first got his telomeres tested in the late 1980s, when he was a professor of biochemistry at McMaster University. He’s been charting them on and off since. At times when he was under stress, “not exercising or eating as well as I should have been,” he saw a slight dip in his telomere length, which motivated him to make changes.

Telome Health will be launching in many countries, including Canada, later this year; a few others are already offering telomere testing, such as Life Length, based in Madrid, and SpectraCell Laboratories, in Houston. (Testing is typically done with a blood sample; Telome Health will use blood and saliva.)

Telomere tests are generally ordered by a doctor or health care professional on behalf of the patient. While Telome Health hasn’t announced how much it will cost, Life Length charges about $590 to physicians, although patients could be asked to pay more. Executive Health Centre in Toronto offers a “telomere performance program” that tests a patient’s telomere length, then prescribes interventions (from lifestyle changes to nutritional supplements or hormone replacement) based on results. “For years, I’ve been explaining to people that lifestyle affects aging, longevity and healthspan,” says chief medical officer Dr. Elaine Chin. “Now I have a marker to say, ‘Here you are on a continuum of telomere length.’ ”

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