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 tracks today.
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.’ ”
Results can vary from lab to lab, depending on which techniques are used. To get around this, Telome Health invested in a large study of healthy people in the San Francisco Bay area to provide a basis for comparison. Instead of simply receiving a technical readout of telomere length, which many might struggle to interpret, patients see how they compare to healthy peers, as well as to a group of people at peak health and fitness, aged 20 to 35. With this, a patient could learn she’s in the 60th percentile for her age and gender, for example, meaning her telomeres are a bit longer than average, as well as how she stacks up against the young, healthiest group.
Given telomeres’ reputation as yardsticks for longevity, these tests can produce a fair bit of anxiety. Shay had his telomeres tested by Life Length. “I’m 67, and my shortest telomeres indicated I was 58.” He wasn’t surprised. “My mother lived to 90; my father to 82; I exercise, I don’t smoke, and I’m not overweight.” But he knows a female journalist in her 30s who did the test and, after being told her telomeres were more like those of a fortysomething woman, was “in tears.” She was a mom to three kids, a smoker, with a husband who was often away, and “terribly stressed out,” which he believes could help account for the result. “Nobody says that, based on one test, you’re going to die tomorrow,” Shay insists. “It’s just a biomarker to tell you something is not right—a tap on your shoulder.”
Greider, based at the Johns Hopkins University School of Medicine, would say this frazzled mother worried needlessly. “Is it helpful to tell people their telomere length? I don’t think it is,” the Nobel laureate says. “They’re spending money to get information that isn’t necessarily meaningful.” A group of 30-year-olds, for example, “will have fairly dramatically different telomere lengths from each other,” and the research hasn’t firmed up exactly what that means. Greider and colleagues work with patients suffering from telomere syndromes—rare inherited diseases that result from being born with insufficient telomerase, and aren’t treated with much success. If a patient’s telomeres fall below the first percentile (meaning 99 per cent of people have longer telomeres than he does), science unequivocally shows he’s at risk, she says. “But right now, nothing correlates, in terms of disease outcome, with being in the 40th percentile, for example. We could know more about that in the future, but not now.”
Lansdorp of the B.C. Cancer Research Centre, who is also scientific director of the European Research Institute for the Biology of Ageing in the Netherlands, agrees. “There is a correlation between telomere length and age,” he says, “but it’s also true that there’s a lot of variation. You see teenagers who have telomeres shorter than a 60-year-old, and the other way round. It becomes difficult to say much.” Lansdorp started a company called Repeat Diagnostics, based in Vancouver, that offers telomere testing—for medical researchers only, not the general public. Blackburn acknowledges there’s still much to learn. Telomere testing is “a statistic. It’s not a crystal ball.”
Stephen Matlin, chief executive officer of Life Length, likens it to tests for another biomarker, cholesterol, which is now standard at the doctor’s office. “When cholesterol testing came out, the test was very simple. It just looked at whole cholesterol and didn’t break it down like it does today.” Back then, no cholesterol drug existed; patients with worrying cholesterol levels had to make changes where they could, to their diet and exercise habits. Years went by, and the test grew more sophisticated. According to Matlin, from 1982 to 1996, cholesterol testing in the U.S. alone “went from zero to 30 million tests a year. But there were still no drugs.” Then Pfizer developed Lipitor, which went on to become the bestselling drug in the history of pharmaceuticals.
Maybe in a decade or so, a telomerase activator will be next to claim that title—the anti-aging industry’s Holy Grail.
Imagine if an elderly person could suddenly build muscle, reverse aging effects in the brain, even grow a thick, healthy head of hair. Something like this was achieved by Dr. Ronald DePinho, who is renowned for his studies on aging, in a study published in Nature in 2010—except he did it in lab mice, by tinkering with their telomerase.
DePinho, who is now president of the University of Texas MD Anderson Cancer Center and was then at Harvard Medical School, wasn’t working with normal mice; his were engineered with a controllable telomerase gene, meaning they could switch it on and off. Without the enzyme, mice became prematurely old. “They developed infertility and shrunken brains,” he says. “Impaired cognition, skeletal problems, heart problems. In that state of severe degeneration, we flipped the switch back on.”
They expected the aging process of these mice to stabilize, but instead, the signs of aging actually seemed to wind backward. “They had improved cognition. They became more active. Their hair coat was restored to a healthy sheen. They became fertile.” After they’d reactivated telomerase for a month, the mice resembled young adults. DePinho called it a “near Ponce de León effect,” after the 16th-century Spanish explorer who went questing after the fountain of youth.
Of course, designer mice aren’t a good stand-in for aging humans. But the study hints at how powerful telomerase can be—and the fact that “tissues retain a remarkable capacity to renew themselves” when the cause of rapid aging was removed. Telomerase, however, is a double-edged sword. People with low levels (and very short telomeres) are at risk of some types of cancer, but on the other hand, too much of it (and overly long telomeres) has been associated with cancer risk, Harley says. Overactive telomerase allows cancer cells to become immortal, multiplying without end, which is why telomerase inhibitors are also a hot area of research.
Given telomerase’s reputation as a fountain of youth, it’s no wonder that “telomerase activators” have found their way to market. TA-65, sold by T.A. Sciences, is one such product. Based on an agent originally discovered and patented by biopharmaceutical company Geron, it’s sold as a nutritional supplement (and doesn’t require approval of the U.S. Food and Drug Administration). According to T.A. Sciences’ founder and chairman, Noel Thomas Patton, it works by flipping on a gene that activates telomerase; about 20,000 people around the world are now taking TA-65, a number that’s growing. It isn’t cheap—one bottle of 90 capsules goes for $600, and people take one to four capsules per day. Patton, 67, who’s taken TA-65 himself for six years, insists that cancer is not a concern: “By strengthening the immune system, [TA-65] is a cancer preventative,” he claims.
Blackburn and other telomere experts caution against supplements. “There’s nothing that’s been clinically validated,” she insists. Until a drug is discovered, she says patients who worry about telomere length can only improve their diet, exercise habits and stress levels, which preliminary and pilot studies suggest could make a difference.
In 2008, a small study was published in The Lancet Oncology suggesting lifestyle changes can increase telomerase activity. Co-authored by Blackburn and Dr. Dean Ornish, who’s also based at UCSF, it followed 30 men with low-risk prostate cancer as they altered their diet, subbing in whole, plant-based foods and supplementing with omega-3 fatty acids. They got moderate exercise, did yoga or meditation for stress management, and joined support groups to bolster their sense of community. After three months, their telomerase activity had increased. Of course, with such a small study, it’s impossible to draw sweeping conclusions, as the scientists themselves noted.
But research is starting to pile up. Other work from Blackburn and colleagues suggest that meditation can boost psychological well-being, which is associated with improvements in telomerase activity. “These studies were small and exploratory,” she emphasizes, “but they’re consistent with each other. They definitely say we should look into this more.”
Exercise, too, has been tied to longer telomeres. “It’s not a huge amount,” Blackburn says. “It’s looking like about 30 minutes that gets you to work up a bit of a sweat, about four or five times a week.” Omega-3 fatty acids found in fish oils have also shown promising results. In a study of elderly men and women with heart disease, Blackburn and cardiologist Dr. Mary Whooley found that having a higher level of these fatty acids at the start of the study was associated with a better subsequent telomere maintenance. Omega-3s help ward off chronic inflammation, Harley explains, “which can cause accelerated telomere loss.”
Finding a drug that could turn telomerase up or down would have all kinds of potential: it could help those patients who suffer from telomere-related diseases, and cancer patients, too. Maybe it could even reverse some of the natural degeneration that comes with age—and stretch the human lifespan, finally defeating the cellular wear and tear, by unlocking anti-aging capabilities that already exist in our cells. As our understanding of telomeres deepens, it seems inevitable that more and more people will live to be healthy centenarians, like Kadonaga, and beyond.
Meanwhile, Kadonaga is enjoying her 101th year. She celebrated her birthday surrounded by family and friends, and is planning a big party—150 guests are invited—to commemorate it again. “I have people say, ‘How did you live so long? Is it diet?—I eat everything and anything—or genes?’ ” (Her oldest brother lived to be 93.) Is it her wide circle of friends and family? Or the fact that she still cooks and cleans for herself? Is it attitude? “My mom isn’t just a glass-half-full kind of person,” says daughter Mona Russell, 58. “To her, the glass is overflowing.”
All of these factors contribute to a long, healthy life, as research continues to affirm—whatever the impact on the length of Kadonaga’s telomeres. She’s looking forward to the future. She wants to keep living alone, with the help of the nurse and cleaning lady who stop in to help, and droves of friends and neighbours. “Sometimes, even making the bed is a nuisance,” Kadonaga says. “And yet I think, ‘I can do it.’ ”