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The mystery of longevity: Scientists reverse engineer vigour to protect against aging

Posted: February 27, 2012 at 1:49 am

Tom Blackwell  Feb 26, 2012 – 1:03 PM ET | Last Updated: Feb 26, 2012 1:12 PM ET

Louise Levy attends regular Tai-chi classes, retired three years ago from her secretarial job and says she would still be driving today if her car had not “conked out before I did.” None of which would be particularly unusual, except Mrs. Levy is 101 years old.

“My mind is still clear and I don’t have a memory problem,” says the resident of Rye, N.Y., about the latest chapter in a life that began when movies were silent and the Model-T Ford cutting edge. “It’s been absolutely marvelous.”

Mrs. Levy’s long and generally healthy life is the focus of a fascinating scientific study, itself at the forefront of a little-noticed but radical approach to medical research. Turning upside down the traditional quest to understand and cure specific diseases, some researchers are examining instead healthy and long-lived humans and animals for their biological secrets.

By reverse engineering the source of that vigour, scientists hope to develop drugs or supplements that could give less genetically fortunate people more protection against the ravages of aging and chronic illness.

Go on, count your blessings

When the U.S. Army wanted to prepare its troops better for the psychological rigours of two bloody wars, it turned to experts behind positive psychology — a movement that strives to figure out what makes people happy — rather than tackle mental illness.

Scientists following the approach probe contented, stress-resistant people for clues to help others flourish emotionally and avoid mental distress. Unlike medical researchers pursuing the newly coined “positive biology,” the psychologists are not typically aiming to develop drugs that can tweak people’s molecular make-up, but discover emotional strategies that enhance mental well-being.

One project is teaching U.S. soldiers methods learned from naturally stress-resilient people, helping them deal better with the strain of military missions.

Sonja Lyubomirsky, a leading positive-psychology researcher at the University of California, has identified some key attributes in the inherently happy and well-adjusted, and finds that imparting those approaches to others can help even some depressed people.
The surprisingly straightforward tactics include counting one’s blessings, being kind to others and expressing gratitude.

A recent experiment on elementary-school children in Vancouver seemed to confirm her findings.

“Of course, it’s important to study mental illness and stress and divorce, anxiety, all the sort of negative things, but I think we have to take a different approach, too,” she said.

National Post
• Email: tblackwell@nationalpost.com

Those researchers struggle now for recognition in a medical establishment hived off into separate wars against individual diseases. A Canadian academic, however, is calling for a tectonic shift toward what he calls “positive biology.” Solving the molecular mysteries of the healthy to stave off disease and aging would make the system “much more efficient,” argues Professor Colin Farrelly of Queen’s University in a recent paper in the journal of the European Molecular Biology Organization.

“We think it will be more important for public health than the introduction of antibiotics,” echoed Jay Olshansky, a public-health professor at the University of Illinois who has promoted a similar concept for several years. “This will be the medical breakthrough of the 21st century when it happens.… It’s going to be huge.”

Continuing to just combat specific diseases, on the other hand, will produce surprisingly modest advances, he contends. While curbing infant mortality and other achievements stretched life spans by 30 years in the 20th century, even a complete cure of all cancers would increase longevity by an average of just more than three years, Prof. Olshansky has estimated.

The argument seems to be slowly gaining some traction, with Canada’s federal medical-research agency saying it is looking seriously at positive biology.

The study that has Mrs. Levy under a microscope is identifying genes linked to long life. Gabrielle Boulianne, a Toronto biologist, and others are unscrambling similar biological puzzles in exceptional specimens of fruit flies, worms and other lower life forms. Canadian infectious-disease experts have studied the lucky few people who seem naturally resistant to HIV infection; and a U.S. clinic is probing the DNA of diabetes patients who stay remarkably free of the disease’s dire complications for decades.

At the core of positive biology is not an attempt to simply identify lifestyle choices — like quitting cigarettes or French fries — that can stave off disease, though those have proven value. The goal instead is to identify the mechanisms by which some people naturally live long and well, then translate that knowledge into pharmaceutical treatments.

The centenarian study at New York’s Albert Einstein College of Medicine has enrolled more than 500 men and women who have lived in good health to 100 or close to it, focusing exclusively on Ashkenazi Jews, not because of any special aging quality, but to avoid ethnic variations that might complicate results. The Einstein researchers have come up with some intriguing findings.

Rather than all being paragons of lifestyle virtue, half the centenarians were overweight or obese, 60% smoked for over 30 years — and one had a tobacco habit that stretched across nine decades, noted Dr. Nir Barzilai, who heads the project.

“It’s all genetics,” he said. “To be 100 years old, it’s strongly genetic.”

Backing up that hypothesis is that many of the centenarians are from families full of similar “super agers;” they include a set of four siblings, all of whom reached at least 102 and one of whom hit 110.

Brian Harkin for National Post

Louise Levy, 101, in her apartment at The Osbourne retirement community.

Mrs. Levy, who lives in a quiet residential community about 25 kilometres north of Manhattan, still clearly remembers the end of the First World War, yet looks decades younger than her birth certificate discloses. She is not convinced, though, that living so long and so well was thanks largely to a genetic windfall. Her mother did survive to an impressive 94, but was rather sickly in her old age, and no other close relatives have enjoyed exceptional aging, she said.

Mrs. Levy smoked for a while when younger and was successfully treated for breast cancer in 1996. She thinks her longevity might stem from the low-cholesterol diet she has followed for 30 years, a positive outlook and, maybe, the one glass of red wine she still downs daily.

“Everybody says ‘good genes,’ ” the mother of two 60-something children said, “but I don’t think it’s good genes.”

The research at Albert Einstein indicates otherwise. Through testing of the centenarians and, for comparison purposes, normally aging people, Dr. Barzilai and colleagues have uncovered several genetic signposts of exceptional longevity: subjects with a particular gene mutation live on average four years longer; the “telomeres” part of the DNA molecule is longer in centenarians; and the hormone “adiponectin” is involved in improvements to insulin production and artery inflammation that are linked to healthy aging.

In the discovery that lies closest to a tangible treatment, they concluded that restricted activity of the “CETP” gene, earlier linked to higher HDL or “good-cholesterol” levels, is also tied to longevity and prevention of Alzheimer’s disease and cognitive decline.

Pharmaceutical companies seeking to raise good cholesterol volumes are now developing CETP-inhibitor drugs, with Merck & Co. in phase-3 human trials of one potential medicine. Nothing in pharmaceuticals is easy, however. It is unclear whether the Merck pill will work safely for its intended purpose, let alone generate other anti-aging wonders hinted at by the centenarian research.

Pfizer Inc. invested a reported $800-million into developing a similar medicine, only to find that it caused dangerous heart side effects that outweighed any benefits.

A lab at Toronto’s Sick Kids Hospital, meanwhile, is peering into the DNA of a different sort of super ager, with wings and six legs. Researchers headed by Dr. Boulianne, a developmental neurobiologist, have found, among other discoveries, that increased activity of certain genes in the neurons of fruit flies leads to “profound” increases in life span — as much as 135% beyond the normal 60 to 80 days.

And, perhaps as important, many of the genetic footprints present in the elderly insects have also been detected in humans who live exceptionally long lives, including those in so-called “blue zones” — like Nova Scotia’s South Shore — with unusual clusters of centenarians, she said.

‘We think it will be more important for public health than the introduction of antibiotics. This will be the medical breakthrough of the 21st century when it happens.… It’s going to be huge’
— Jay Olshansky, public-health professor at the University of Illinois

“It’s not just that they live longer — because living longer is not attractive to most people if you’re going to spend the last 50 years in a wheelchair or in bed — but the period of time that they’re healthy is also extended,” Dr. Boulianne said. “So the flies, for example, have better locomotion — they can move around better, for longer periods of time, compared to normal flies. And they also have improved cognition, they have better learning and memory.”

As with the findings from the centenarian studies, other researchers are trying to develop drugs that mimic the activity of genes identified by the Toronto lab and others working with such animals.

In Boston, the Harvard-­affiliated Joslin Diabetes Center is examining more than 500 patients who have lived for at least 50 years with potentially deadly, type-1 diabetes, but escaped common complications like blindness and heart and kidney disease. They have already found genetic trademarks that seem to protect against some of those problems.

It still can be a challenge, though, for some practicing positive biology to scrape together research cash, given that funding bodies tend to organize around study of illness itself, with countless careers and reputations tied to success in battling those conditions.

No advocate of the study-the-healthy concept suggests that research on diseases themselves should end — not least because conditions like cancer can afflict the very young — but urge more attention and funding for their approach. “We’ve reached a turning point where we need to expand the tool box,” said Prof. Farrelly of Queen’s.

Meantime, targeting sickness the traditional way will pay limited dividends because, essentially, a normally aging person who is saved from one illness will likely succumb to another relatively soon after, Prof. Olshansky said. The key is to slow down the aging process itself, he said.

“When all you do is attack independent diseases, you leave old age untouched,” Prof. Olshansky said. “You’re basically pushing people into regions of lifetime where other things go wrong.”

The federal government’s main health-research funding body is now hammering together its next five-year plan and is taking positive biology and similar ideas “into very serious consideration,” said Dr. Yves Joanette, head of the Canadian Institutes for Health Research’s institute of aging.

“Healthy and happy at 100 is not necessarily normal,” he said. “It is important to understand exceptional individuals.”

National Post
• Email: tblackwell@nationalpost.com

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The mystery of longevity: Scientists reverse engineer vigour to protect against aging


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