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(CNN) -- It's seven in the morning on the beach in
Santa Monica, California. The low sun glints off the waves and the
clouds are still golden from the dawn. The view stretches out over
thousands of miles of Pacific Ocean. In the distance, white villas of
wealthy Los Angeles residents dot the Hollywood hills. Here by the
shore, curlews and sandpipers cluster on the damp sand. A few meters
back from the water's edge, a handful of people sit cross-legged:
members of a local Buddhist center about to begin an hour-long silent
meditation.
Such spiritual practices
may seem a world away from biomedical research, with its focus on
molecular processes and repeatable results. Yet just up the coast, at
the University of California, San Francisco (UCSF), a team led by a
Nobel Prize-winning biochemist is charging into territory where few
mainstream scientists would dare to tread. Whereas Western biomedicine
has traditionally shunned the study of personal experiences and emotions
in relation to physical health, these scientists are placing state of
mind at the center of their work. They are engaged in serious studies
hinting that meditation might -- as Eastern traditions have long claimed
-- slow aging and lengthen life.
Nobel Prize
Elizabeth Blackburn has always been fascinated by how life works.
Born in 1948, she grew up by the sea in a remote town in Tasmania,
Australia, collecting ants from her garden and jellyfish from the beach.
When she began her scientific career, she moved on to dissecting living
systems molecule by molecule. She was drawn to biochemistry, she says,
because it offered a thorough and precise understanding "in the form of
deep knowledge of the smallest possible subunit of a process."
Yoga practitioners at the 2011 Bali Spirit Festival.
Courtesy SONNY TUMBELAKA/AFP/Getty Images.
Working with biologist
Joe Gall at Yale in the 1970s, Blackburn sequenced the chromosome tips
of a single-celled freshwater creature called Tetrahymena ("pond scum,"
as she describes it) and discovered a repeating DNA motif that acts as a
protective cap. The caps, dubbed telomeres, were subsequently found on
human chromosomes too. They shield the ends of our chromosomes each time
our cells divide and the DNA is copied, but they wear down with each
division. In the 1980s, working with graduate student Carol Greider at
the University of California, Berkeley, Blackburn discovered an enzyme
called telomerase that can protect and rebuild telomeres. Even so, our
telomeres dwindle over time. And when they get too short, our cells
start to malfunction and lose their ability to divide -- a phenomenon
that is now recognized as a key process in aging. This work ultimately
won Blackburn the 2009 Nobel Prize in Physiology or Medicine.
I was interested in the idea that if we look deep within cells we
might be able to measure the wear and tear of stress and daily life.
Elissa Epel, University of California, San Francisco
Elissa Epel, University of California, San Francisco
In 2000, she received a
visit that changed the course of her research. The caller was Elissa
Epel, a postdoc from UCSF's psychiatry department. Psychiatrists and
biochemists don't usually have much to talk about, but Epel was
interested in the damage done to the body by chronic stress, and she had
a radical proposal.
Epel, now director of the
Aging, Metabolism and Emotion Center at UCSF, has a long-standing
interest in how the mind and body relate. She cites as influences both
the holistic health guru Deepak Chopra and the pioneering biologist Hans
Selye, who first described in the 1930s how rats subjected to long-term
stress become chronically ill. "Every stress leaves an indelible scar,
and the organism pays for its survival after a stressful situation by
becoming a little older," Selye said.
Back in 2000, Epel wanted
to find that scar. "I was interested in the idea that if we look deep
within cells we might be able to measure the wear and tear of stress and
daily life," she says. After reading about Blackburn's work on aging,
she wondered if telomeres might fit the bill.
With some trepidation at
approaching such a senior scientist, the then postdoc asked Blackburn
for help with a study of mothers going through one of the most stressful
situations that she could think of -- caring for a chronically ill
child. Epel's plan was to ask the women how stressed they felt, then
look for a relationship between their state of mind and the state of
their telomeres. Collaborators at the University of Utah would measure
telomere length, while Blackburn's team would measure levels of
telomerase.
Nobel Prize-winner Elizabeth Blackburn is spearheading research into the aging effects of stress.
Nobel Prize-winner Elizabeth Blackburn is spearheading research into the aging effects of stress.
Courtesy Justin Sullivan/Getty Images.
Blackburn's research until this point had involved elegant, precisely controlled experiments in the lab. Epel's work, on the other hand, was on real, complicated people living real, complicated lives. "It was another world as far as I was concerned," says Blackburn. At first, she was doubtful that it would be possible to see any meaningful connection between stress and telomeres. Genes were seen as by far the most important factor determining telomere length, and the idea that it would be possible to measure environmental influences, let alone psychological ones, was highly controversial. But as a mother herself, Blackburn was drawn to the idea of studying the plight of these stressed women. "I just thought, how interesting," she says. "You can't help but empathize."
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It took four years
before they were finally ready to collect blood samples from 58 women.
This was to be a small pilot study. To give the highest chance of a
meaningful result, the women in the two groups -- stressed mothers and
controls -- had to match as closely as possible, with similar ages,
lifestyles and backgrounds. Epel recruited her subjects with meticulous
care. Still, Blackburn says, she saw the trial as nothing more than a
feasibility exercise. Right up until Epel called her and said, "You
won't believe it."
The results were crystal
clear. The more stressed the mothers said they were, the shorter their
telomeres and the lower their levels of telomerase.
The most frazzled women
in the study had telomeres that translated into an extra decade or so of
aging compared to those who were least stressed, while their telomerase
levels were halved. "I was thrilled," says Blackburn. She and Epel had
connected real lives and experiences to the molecular mechanics inside
cells. It was the first indication that feeling stressed doesn't just
damage our health -- it literally ages us.
Explosion of research
Unexpected discoveries naturally meet skepticism. Blackburn
and Epel struggled initially to publish their boundary-crossing paper.
"Science [one of the world's leading scientific journals] couldn't
bounce it back fast enough!" chuckles Blackburn.
When the paper finally was published, in the Proceedings of the National Academy of Sciences in December 2004, it sparked widespread press coverage as well as praise.
Robert Sapolsky, a
pioneering stress researcher at Stanford University and author of the
bestselling "Why Zebras Don't Get Ulcers," described the collaboration
as "a leap across a vast interdisciplinary canyon." Mike Irwin, director
of the Cousins Center for Psychoneuroimmunology at the University of
California, Los Angeles, says it took a lot of courage for Epel to seek
out Blackburn. "And a lot of courage for Liz [Blackburn] to say yes."
Buddhist monks practice walking meditation at the Thamkrabok monastery in Phraputthabat, Thailand.
Courtesy NICOLAS ASFOURI/AFP/Getty Images.
Many telomere
researchers were wary at first. They pointed out that the study was
small, and questioned the accuracy of the telomere length test used.
"This was a risky idea back then, and in some people's eyes unlikely,"
explains Epel. "Everyone is born with very different telomere lengths
and to think that we can measure something psychological or behavioral,
not genetic, and have that predict the length of our telomeres? This is
really not where this field was 10 years ago."
Every stress leaves an indelible scar, and the organism pays for
its survival after a stressful situation by becoming a little older.
Hans Selye, pioneering biologist
Hans Selye, pioneering biologist
The paper triggered an
explosion of research. Researchers have since linked perceived stress to
shorter telomeres in healthy women as well as in Alzheimer's
caregivers, victims of domestic abuse and early life trauma, and people
with major depression and post-traumatic stress disorder. "Ten years on,
there's no question in my mind that the environment has some
consequence on telomere length," says Mary Armanios, a clinician and
geneticist at Johns Hopkins School of Medicine who studies telomere
disorders.
There is also progress
towards a mechanism. Lab studies show that the stress hormone cortisol
reduces the activity of telomerase, while oxidative stress and
inflammation -- the physiological fallout of psychological stress --
appear to erode telomeres directly.
This seems to have
devastating consequences for our health. Age-related conditions from
osteoarthritis, diabetes and obesity to heart disease, Alzheimer's and
stroke have all been linked to short telomeres.
The big question for
researchers now is whether telomeres are simply a harmless marker of
age-related damage (like grey hair, say) or themselves play a role in
causing the health problems that plague us as we age. People with
genetic mutations affecting the enzyme telomerase, who have much shorter
telomeres than normal, suffer from accelerated-aging syndromes and
their organs progressively fail. But Armanios questions whether the
smaller reductions in telomere length caused by stress are relevant for
health, especially as telomere lengths are so variable in the first
place.
Blackburn, however, says
she is increasingly convinced that the effects of stress do matter.
Although the genetic mutations affecting the maintenance of telomeres
have a smaller effect than the extreme syndromes Armanios studies,
Blackburn points out that they do increase the risk of chronic disease
later in life. And several studies have shown that our telomeres predict
future health. One showed
that elderly men whose telomeres shortened over two-and-a-half years
were three times as likely to die from cardiovascular disease in the
subsequent nine years as those whose telomeres stayed the same length or
got longer.
Ten years on, there's no question in my mind that the environment has some consequence on telomere length,
Mary Armanios, Johns Hopkins School of Medicine
Mary Armanios, Johns Hopkins School of Medicine
In another study, looking at over 2,000 healthy Native Americans,
those with the shortest telomeres were more than twice as likely to
develop diabetes over the next five-and-a-half years, even taking into
account conventional risk factors such as body mass index and fasting
glucose.
Blackburn is now moving
into even bigger studies, including a collaboration with healthcare
giant Kaiser Permanente of Northern California that has involved
measuring the telomeres of 100,000 people. The hope is that combining
telomere length with data from the volunteers' genomes and electronic
medical records will reveal additional links between telomere length and
disease, as well as more genetic mutations that affect telomere length.
The results aren't published yet, but Blackburn is excited about what
the data already shows about longevity. She traces the curve with her
finger: as the population ages, average telomere length goes down. This
much we know; telomeres tend to shorten over time. But at age 75--80,
the curve swings back up as people with shorter telomeres die off --
proof that those with longer telomeres really do live longer. "It's
lovely," she says. "No one has ever seen that."
In the decade since
Blackburn and Epel's original study, the idea that stress ages us by
eroding our telomeres has also permeated popular culture. In addition to
Blackburn's many scientific accolades, she was named one of Time
magazine's "100 most influential people in the world" in 2007, and
received a "Good Housekeeping" achievement award in 2011. A workaholic
character played by Cameron Diaz even described the concept in the 2006
Hollywood film "The Holiday." "It resonates," says Blackburn.
But as evidence of the damage caused by dwindling telomeres piles up, she is embarking on a new question: how to protect them.
Mindfulness meditation
At first, the beach seems busy. Waves
splash and splash and splash. Sanderlings wheel along the shoreline.
Joggers and dog walkers amble across, while groups of pelicans hang out
on the water before taking wing or floating out of sight. A surfer,
silhouetted black against the sky, bobs about for 20 minutes or so,
catching the odd ripple towards shore before he, too, is gone. The
unchanging perspective gives a curious sense of detachment. You can
imagine that the birds and joggers and surfers are like thoughts: they
inhabit different forms and timescales but in the end, they all pass.
Girls meditating at a Buddhist monastic school in Myanmar.
Courtesy NICOLAS ASFOURI/AFP/Getty Images.
There are hundreds of
ways to meditate but this morning I'm trying a form of Buddhist
mindfulness meditation called open monitoring, which involves paying
attention to your experience in the present moment. Sit upright and
still, and simply notice any thoughts that arise -- without judging or
reacting to them -- before letting them go. For Buddhists this is a
spiritual quest; by letting trivial thoughts and external influences
fall away, they hope to get closer to the true nature of reality.
Blackburn too is
interested in the nature of reality, but after a career spent focusing
on the measurable and quantifiable, such navel-gazing initially held
little personal appeal and certainly no professional interest. "Ten
years ago, if you'd told me that I would be seriously thinking about
meditation, I would have said one of us is loco," she told the New York
Times in 2007. Yet that is where her work on telomeres has brought her.
Since her initial study with Epel, the pair have become involved in
collaborations with teams around the world -- as many as 50 or 60,
Blackburn estimates, spinning in "wonderful directions." Many of these
focus on ways to protect telomeres from the effects of stress; trials
suggest that exercise, eating healthily and social support all help. But
one of the most effective interventions, apparently capable of slowing
the erosion of telomeres -- and perhaps even lengthening them again --
is meditation.
So far the studies are small, but they all tentatively point in the same direction. In one ambitious project,
Blackburn and her colleagues sent participants to meditate at the
Shambhala mountain retreat in northern Colorado. Those who completed a
three-month course had 30% higher levels of telomerase than a similar
group on a waiting list.
I do think that in general we've got a society with scattered
attention, particularly when people are highly stressed and don't have
the resources to just be present wherever they are.
Elissa Epel, University of California, San Francisco
Elissa Epel, University of California, San Francisco
A pilot study of dementia caregivers,
carried out with UCLA's Irwin and published in 2013, found that
volunteers who did an ancient chanting meditation called Kirtan Kriya,
12 minutes a day for eight weeks, had significantly higher telomerase
activity than a control group who listened to relaxing music.
And a collaboration with UCSF physician and self-help guru Dean Ornish,
also published in 2013, found that men with low-risk prostate cancer
who undertook comprehensive lifestyle changes, including meditation,
kept their telomerase activity higher than similar men in a control
group and had slightly longer telomeres after five years.
In their latest study,
Epel and Blackburn are following 180 mothers, half of whom have a child
with autism. The trial involves measuring the women's stress levels and
telomere length over two years, then testing the effects of a short
course of mindfulness training, delivered with the help of a mobile app.
Theories differ as to
how meditation might boost telomeres and telomerase, but most likely it
reduces stress. The practice involves slow, regular breathing, which may
relax us physically by calming the fight-or-flight response. It
probably has a psychological stress-busting effect too. Being able to
step back from negative or stressful thoughts may allow us to realize
that these are not necessarily accurate reflections of reality but
passing, ephemeral events. It also helps us to appreciate the present
instead of continually worrying about the past or planning for the
future.
"Being present in your
activities and in your interactions is precious, and it's rare these
days with all of the multitasking we do," says Epel. "I do think that in
general we've got a society with scattered attention, particularly when
people are highly stressed and don't have the resources to just be
present wherever they are."
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Ruffling feathers
Inevitably, when a Nobel Prize-winner starts talking about meditation, it ruffles a few feathers. In
general, Blackburn's methodological approach to the topic has earned a
grudging admiration, even among those who have expressed concern about
the health claims made for alternative medicine. "She goes about her
business in a cautious and systematic fashion," says Edzard Ernst of the
University of Exeter, UK, who specializes in testing complementary
therapies in rigorous controlled trials. Oncologist James Coyne of the
University of Pennsylvania, Philadelphia, who is skeptical of this field
in general and describes some of the research on positive psychology
and health as "morally offensive" and "tooth fairy science," concedes
that some of Blackburn's data is "promising."
Others aren't so
impressed. Surgeon-oncologist David Gorski is a well-known critic of
alternative medicine and pseudoscience who blogs under the name of Orac
-- he's previously described Dean Ornish as "one of the four horsemen of
the Woo-pocalypse." Gorski stops short of pronouncing meditation as
off-limits for scientific inquiry, but expresses concern that the
preliminary results of these studies are being oversold. How can you be
sure you're investigating it rigorously? "It's really hard to do with
these things," he says. "It is easy to be led astray. Nobel
Prize-winners are not infallible." Blackburn's own biochemistry
community also seems ambivalent about her interest in meditation. Three
senior telomere researchers I contacted declined to discuss this aspect
of her work, with one explaining that he didn't want to comment "on such
a controversial issue."
"People are very
uncomfortable with the concept of meditation," notes Blackburn. She
attributes this to its unfamiliarity and its association with spiritual
and religious practices. "We're always trying to say it as carefully as
we can... always saying 'look, it's preliminary, it's a pilot.' But
people won't even read those words. They'll see the newspaper headings
and panic."
Meditation has become increasingly popular in the West since the 1960s.
Any connotation of
religious or paranormal beliefs makes many scientists uneasy, says Chris
French, a psychologist at Goldsmiths, University of London, who studies
anomalous experiences including altered states of consciousness. "There
are a lot of raised eyebrows, even though I've got the word skeptic
virtually tattooed across my forehead," he says.
"It smacks of new-age woolly ideas for some people.
There's a kneejerk dismissive response of 'we all know it's nonsense, why are you wasting your time?'"
"It smacks of new-age woolly ideas for some people.
There's a kneejerk dismissive response of 'we all know it's nonsense, why are you wasting your time?'"
"When meditation first
came to the West in the 1960s it was tied to the drug culture, the
hippie culture," adds Sara Lazar, a neuroscientist at Harvard who
studies how meditation changes the structure of the brain. "People think
it's just a bunch of crystals or something, they roll their eyes." She
describes her own decision to study meditation, made 15 years ago, as
"brave or crazy," and says that she only plucked up the courage because
at around the same time, the U.S. National Institutes of Health (NIH)
created the National Center for Complementary and Alternative Medicine.
"That gave me the confidence thmat I could do this and I would get
funding."
The tide is now turning.
Helped in part by that NIH money, researchers have developed
secularized -- or non-religious -- practices such as mindfulness-based
stress reduction and mindfulness-based cognitive therapy, and reported a
range of health effects from lowering blood pressure and boosting
immune responses to warding off depression. And the past few years have
seen a spurt of neuroscience studies, like Lazar's, showing that even
short courses of meditation can forge structural changes in the brain.
Now that the brain data and all this clinical data are coming out,
that is starting to change. People are a lot more accepting [of
meditation].
Sara Lazar, Harvard University
Sara Lazar, Harvard University
"Now that the brain data and all this clinical data are coming out, that is starting to change. People are a lot more accepting [of meditation]," says Lazar. "But there are still some people who will never believe that it has any benefit whatsoever."
Blackburn's view is that meditation is a fair topic to study, as long as robust methods are used. So when her research first pointed in this direction, she was undaunted by concerns about what such studies might do to her reputation. Instead, she tried it out for herself, on an intensive six-day retreat in Santa Barbara. "I loved it," she says. She still uses short bursts of meditation, which she says sharpen her mind and help her to avoid a busy, distracted mode. She even began one recent paper with a quote from the Buddha: "The secret of health for both mind and body is not to mourn for the past, worry about the future, or anticipate troubles but to live in the present moment wisely and earnestly."
That study, of 239 healthy women, found that those whose minds wandered less -- the main aim of mindfulness meditation -- had significantly longer telomeres than those whose thoughts ran amok.
"Although we report
merely an association here, it is possible that greater presence of mind
promotes a healthy biochemical milieu and, in turn, cell longevity,"
the researchers concluded. Contemplative traditions from Buddhism to
Taoism believe that presence of mind promotes health and longevity;
Blackburn and her colleagues now suggest that the ancient wisdom might
be right.
"Medicine Buddha"
I meet with Blackburn in Paris. We're
at an Art Nouveau-themed bistro just down the road from the Curie
Institute, where she is on a short sabbatical, arranging seminars
between groups of scientists who don't usually talk to one another. In a
low, melodious voice that I strain to hear through the background
clatter, the 65-year old tells me of her first major brush with Buddhist
thinking.
In September 2006, she
attended a conference held at the Menla Mountain Buddhist center, a
remote retreat in New York's Catskill mountains, at which Western
scientists met with Tibetan-trained scholars including the Dalai Lama to
discuss longevity, regeneration and health. During the meeting, the
spiritual leader honored Blackburn's scientific achievements by
inducting her as a "Medicine Buddha."
Tibetan spiritual leader the Dalai Lama (here in Tokyo) inducted Blackburn as a "Medicine Buddha."
Couresty Keith Tsuji/Getty Images.
If Epel's psychiatry
research had been another world, the scholars' Eastern philosophy seemed
to Blackburn more alien still. Over dinner one evening, while
explaining to the other delegates how errors in the gene for telomerase
can cause health problems, she described genetic mutation as a random,
chance event. That's dogma for Western scientists but not for those
trained in the Tibetan worldview. "They said 'oh no, we don't regard
this as chance,'" says Blackburn. For these holistic scholars, even the
smallest events were infused with meaning. "I suddenly thought, whoa,
this is a very different world from the one I'm on."
But instead of
dismissing her Eastern counterparts, she was impressed, finding the
Dalai Lama to have "a very good brain," for example. "They're scholarly
in a very different way, but it is still good-quality thinking," she
explains. "It wasn't 'God told me this,' it was more 'let's see what
actually happens in the brain.' So there are certain elements of the
approach that I am quite comfortable with as a scientist."
Blackburn isn't tempted
to embrace the spiritual approach herself. "I'm rooted in the physical
world," she says. But she combines that grounding with an open mind
towards new ideas and connections, and she seems to love breaking out of
established paradigms. For example, she and Epel have shown that the
effects of stress on telomeres can be passed on to the next generation.
If women experience stress while pregnant, their children have shorter
telomeres, as newborns and as adults -- in direct contradiction of the
standard view that traits can only be passed on via our genes.
In the future,
information from telomeres may help doctors decide when to prescribe
particular drugs. For example, telomerase activity predicts who will
respond to treatment for major depression, while telomere length
influences the effects of statins. In general, however, Blackburn is
more interested in how telomeres might help people directly, by
encouraging them to live in a way that reduces their disease risk. "This
is not a familiar model for the medical world," she says.
It's now a consistent story that the aging machinery is shaped at the earliest stages of life.
Elizabeth Blackburn, University of California, San Francisco
Elizabeth Blackburn, University of California, San Francisco
Conventional medical
tests give us our risk of particular conditions -- high cholesterol
warns of impending heart disease, for example, while high blood sugar
predicts diabetes. Telomere length, by contrast, gives an overall
reading of how healthy we are: our biological age. And although we
already know that we should exercise, eat well and reduce stress, many
of us fall short of these goals. Blackburn believes that putting a
concrete number on how we are doing could provide a powerful incentive
to change our behaviour. In fact, she and Epel have just completed a
study (as yet unpublished) showing that simply being told their telomere
length caused volunteers to live more healthily over the next year than
a similar group who weren't told.
Ultimately, however, the
pair want entire countries and governments to start paying attention to
telomeres. A growing body of work now shows that the stress from social
adversity and inequality is a major force eroding these protective
caps. People who didn't finish high school or are in an abusive
relationship have shorter telomeres, for example, while studies have
also shown links with low socioeconomic status, shift work, lousy
neighborhoods and environmental pollution. Children are particularly at
risk: being abused or experiencing adversity early in life leaves people
with shorter telomeres for the rest of their lives. And through
telomeres, the stress that women experience during pregnancy affects the
health of the next generation too, causing hardship and economic costs
for decades to come.
In 2012, Blackburn and Epel wrote a commentary in the journal Nature, listing some of these results and calling on politicians to prioritize "societal stress reduction."
Metabolism and aging: What you can do
In particular, they
argued, improving the education and health of women of child-bearing age
could be "a highly effective way to prevent poor health filtering down
through generations." Meditation retreats or yoga classes might help
those who can afford the time and expense, they pointed out. "But we are
talking about broad socioeconomic policies to buffer the chronic
stressors faced by so many." Where many scientists refrain from
discussing the political implications of their work, Blackburn says she
wanted to speak out on behalf of women who lack support, and say "You'd
better take their situations seriously."
While arguments for
tackling social inequality are hardly new, Blackburn says that telomeres
allow us to quantify for the first time the health impact of stress and
inequality and therefore the resulting economic costs. We can also now
pinpoint pregnancy and early childhood as "imprinting periods" when
telomere length is particularly susceptible to stress. Together, she
says, this evidence makes a stronger case than ever before for
governments to act.
But it seems that most
scientists and politicians still aren't ready to leap across the
interdisciplinary canyon that Blackburn and Epel bridged a decade ago.
The "Nature" article has engendered little response, according to a
frustrated Epel. "It's a strong statement so I would have thought that
people would have criticized it or supported it," she says. "Either
way!"
"It's now a consistent
story that the aging machinery is shaped at the earliest stages of
life," she insists. "If we ignore that and we just keep trying to put
band-aids on later, we're never going to get at prevention and we're
only going to fail at cure." Simply responding to the physical symptoms
of disease might make sense for treating an acute infection or fixing a
broken leg, but to beat chronic age-related conditions such as diabetes,
heart disease and dementia, we will need to embrace the fuzzy,
subjective domain of the mind.
Copyright 2014 The Wellcome Trust. Some rights reserved.
