Physical Activity Has Anti-Aging Effect on
Cardiovascular System: German Study
Utah scientist reports on emerging importance of
telomeres in aging, cancer and maybe immortality;
seniors with short telomeres most likely to die – see below
story
Fluorescence-stained
chromosomes (red) on a microscope slide. Telomere sequences (yellow)
reside at the ends of each chromosome. More about telomeres from
University of Utah below main story.
Dec. 1, 2009 – People who engage in regular
physical activity are gaining an anti-aging weapon that will help them
live longer lives. New research finds intensive exercise prevents aging
of the cardiovascular system by preventing shortening of telomeres – the
DNA that bookends the chromosomes and protects the ends from damage, a
protective effect against aging.
Researchers report in Circulation: Journal of
the American Heart Association that they measured the length of
telomeres in blood samples from two groups of professional athletes and
two groups who were healthy nonsmokers, but not regular exercisers.
The telomere shortening mechanism limits cells to a
fixed number of divisions and can be regarded as a “biological clock.”
Gradual shortening of telomeres through cell divisions leads to aging on
the cellular level and may limit lifetimes. When the telomeres become
critically short the cell undergoes death.
The 2009 Nobel Prize in Physiology or Medicine was
awarded to researchers who discovered the nature of telomeres and how
chromosomes are protected by telomeres and the enzyme telomerase.
“The most significant finding of this study is that
physical exercise of the professional athletes leads to activation of
the important enzyme telomerase and stabilizes the telomere,” said
Ulrich Laufs, M.D., the study’s lead author and professor of clinical
and experimental medicine in the department of internal medicine at
Saarland University in Homburg, Germany.
“This is direct evidence of an anti-aging effect of
physical exercise. Physical exercise could prevent the aging of the
cardiovascular system, reflecting this molecular principle.”
Essentially, the longer telomere of athletes is an
efficient telomere.
The body’s cells are constantly growing and
dividing and eventually dying off, a process controlled by the
chromosomes within each cell. These chromosomal “end caps” — which have
been likened to the tips of shoelaces, preventing them from fraying —
become shorter with each cell division, and when they’re gone, the cell
dies. Short telomeres limit the number of cell divisions, Laufs said.
In addition, the animal studies of Laufs and
colleagues show that the regulation of telomere stabilizing proteins by
exercise exerts important cellular functions beyond the regulation of
telomere length itself by protecting from cellular deterioration and
programmed cell death.
In the clinical study, researchers analyzed 32
professional runners, average age 20, from the German National Team of
Track and Field. Their average running distance was about 73 kilometers
(km), a little over 45 miles, per week.
Researchers compared the young professional
athletes with middle-aged athletes with a history of continuous
endurance exercise since their youth. Their average age was 51 and their
average distance was about 80 km, or almost 50 miles, per week.
The two groups were evaluated against untrained
athletes who were healthy nonsmokers, but who did not exercise
regularly. They were matched for age with the professional athletes.
The fitness level of the athletes was superior to
the untrained individuals. The athletes had a slower resting heart rate,
lower blood pressure and body mass index, and a more favorable
cholesterol profile, researchers said.
Long-term exercise training activates telomerase
and reduces telomere shortening in human leukocytes. The age-dependent
telomere loss was lower in the master athletes who had performed
endurance exercising for several decades.
“Our data improves the molecular understanding of
the protective effects of exercise on the vessel wall and underlines the
potency of physical training in reducing the impact of age-related
disease,” Laufs said.
The German Research Association and the University
of Saarland funded the study.
Co-authors are: Christian Werner, M.D.; Tobias
Furster, medical student; Thomas Widmann, M.D.; Janine Pöss, M.D.;
Christiana Roggia, Ph. D.; Milad Hanhoun, M.D.; Jürgen Scharhag, M.D.;
Nicole Buchner, Ph. D.; Tim Meyer, M.D.; Willfried Kindermann, M.D.;
Judith Haendeler, Ph. D. and Michael Böhm, M.D.
Additional Resources:
• The American Heart Association’s Start! initiative encourages all
Americans to participate in regular physical activity. Start! includes
personalized walking plans for people at any fitness level. Visit
www.startwalkingnow.org to download the Start! Walking Plans and
locate Start! Walking Paths near you.
Are Telomeres the Key to Aging and Cancer?
Inside the center or nucleus of a cell, our genes
are located on twisted, double-stranded molecules of DNA called
chromosomes. At the ends of the chromosomes are stretches of DNA called
telomeres, which protect our genetic data, make it possible for cells to
divide and hold some secrets to how we age and get cancer.
Telomeres have been compared with the plastic tips
on shoelaces because they prevent chromosome ends from fraying and
sticking to each other, which would scramble an organism's genetic
information to cause cancer, other diseases or death.
Yet, each time a cell divides, the telomeres get
shorter. When they get too short, the cell no longer can divide and
becomes inactive or "senescent" or dies. This process is associated with
aging, cancer and a higher risk of death. So telomeres also have been
compared with a bomb fuse.
… What role do telomeres play in cancer?
As a cell begins to become cancerous, it divides
more often, and its telomeres become very short. If its telomeres get
too short, the cell may die. It can escape this fate by becoming a
cancer cell and activating an enzyme called telomerase, which prevents
the telomeres from getting even shorter.
Studies have found shortened telomeres in many
cancers, including pancreatic, bone, prostate, bladder, lung, kidney,
and head and neck.
Measuring telomerase may be a new way to detect
cancer.
… What about telomeres and aging?
Geneticist Richard Cawthon and colleagues at the
University of Utah found shorter telomeres are associated with shorter
lives. Among people older than 60, those with shorter telomeres were
three times more likely to die from heart disease and eight times more
likely to die from infectious disease.
While telomere shortening has been linked to the
aging process, it is not yet known whether shorter telomeres are just a
sign of aging - like gray hair - or actually contribute to aging….
… How big a role do telomeres play in aging?
Some long-lived species like humans have telomeres
that are much shorter than species like mice, which live only a few
years. Nobody yet knows why. But it's evidence that telomeres alone do
not dictate lifespan.
Cawthon's study found that when people are divided
into two groups based on telomere lengths, the half with longer
telomeres lives five years longer than those with shorter telomeres.
That suggests lifespan could be increased five years by increasing the
length of telomeres in people with shorter ones.
Chromosome Ends
Shorten with Age, Predict Mortality from Heart
Disease, Various Infectious Diseases
News release from 2003 issued by The Lancet on research from the U of Utah
School of Medicine's Department of Human
Genetics, Huntsman Cancer Institute, and
Department of Family and Consumer Studies
Once a person is older than 60, their risk of death
doubles with every eight years of age. So a 68-year-old has twice the
chance of dying within a year compared with a 60-year-old. Cawthon's
study found that differences in telomere length accounted for only 4
percent of that difference.
And while intuition tells us older people
have a higher risk of death, only another 6 percent is due purely to
chronological age. When telomere length, chronological age and gender
are combined (women live longer than men), those factors account for 37
percent of the variation in the risk of dying over age 60. So what
causes the other 63 percent?
January 30, 2003 -- As if it's not bad enough
that people lose their hair, teeth, and eyesight
as they age, their chromosomes desert them, too.
As people get older, telomeres-the ends of
chromosomes-get shorter in all dividing cells in
the body, except the germline (cells from which
a new organism can develop).
This, according to
University of Utah medical researchers, holds
major health implications for people over age 60
because shortened telomeres in blood are
associated with increased risks of dying from
heart disease or infectious diseases.
In a study published in the February 1 issue of
the international medical journal, The Lancet,
researchers from the U of Utah School of Medicine's
Department of Human Genetics, Huntsman Cancer
Institute, and Department of Family and Consumer
Studies concluded that women and men with
shorter telomeres died sooner than people with
longer telomeres.
Women with shorter telomeres
died a median 4.8 years sooner, while men died a
median 4 years earlier than their counterparts.
"Telomere length was a significant predictor of
mortality in people ages 60 to 74," said Richard
M. Cawthon, M.D., Ph.D., research assistant
professor of human genetics and lead author of
the study.
In people age 75 and older, telomere length was
a moderate predictor of mortality.
The researchers studied 143 unrelated Utah
residents, ages 60 to 97, who donated blood from
1982-1986. At the time the study concluded, 101
of the people had died.
People whose telomere length was in the bottom
half of the study group had a heart disease
mortality rate more than three times higher than
subjects whose telomere length was in the top
half, the researchers found.
Those with telomere length in the bottom quarter
had an infectious disease mortality rate eight
times higher than people in the top
three-quarters for telomere length.
"Overall, individuals with shorter telomeres had
nearly twice the mortality rate of people with
longer telomeres," Cawthon said.
Telomere length is measured in base pairs of
DNA. The average length at birth is 8,000, but
as people age, the average drops to around 3,000
base pairs. Telomere lengths of those in the
study ranged from 1,930 to 4310 base pairs.
Although the study correlated telomere length
with increased heart disease and infectious
disease mortality, the researchers still aren't
sure exactly what that means. But the study
findings raised three possibilities:
-- Shorter telomeres increase disease mortality
risks and it's possible that a medical
intervention to lengthen telomeres could
increase longevity.
-- Shorter telomeres do not increase the risk of
dying, but are markers of an underlying cause of
heart disease and infectious disease, perhaps a
fundamental process of aging.
-- People in the study with shorter telomeres
already were ill and telomere length was simply
a sign of disease.
"The most exciting possibility suggested by the
study is that if we could do some sort of
medical intervention and lengthen people's
telomeres, they would live longer and healthier
lives," Cawthon said.
It may be possible, for example, to introduce
the gene that produces the enzyme that makes
telomeres longer.
Even if short telomeres do not raise mortality
risks directly, but are merely a marker of an
underlying cause of age-related disease,
measurements of telomere length still may lead
researchers to the genes that regulate rates of
aging in people, according to Cawthon.
Telomere shortening is accelerated in
dyskeratosis congenita, a genetic disorder in
which patients suffer premature onset of
multiple age-related diseases. The median age of
death for people with the disorder is 16.
The Utah researchers had hypothesized that
telomere shortening in people without the
disorder also would contribute to mortality in
multiple age-related diseases.
Evan C. Hadley, M.D., associate director of
geriatrics and clinical gerontology at the
National Institute on Aging of the National
Institutes of Health (NIH), said the study bears
follow-up.
"This is a very interesting finding … But, as
the authors note, the association between
telomere length and mortality doesn't prove that
telomeres cause increased mortality risk-they
may just be a marker, reflecting other processes
that are the real culprits," Hadley said. "We
need further study to clarify this."
The NIA provided funding for the study.
Along with Cawthon, the researchers included Ken
R. Smith, Ph.D., professor of family and
consumer studies; Elizabeth O'Brien, Ph.D., and
Anna Sivatchenko, M.D., of the Huntsman Cancer
Institute at the University of Utah; and Richard
A. Kerber, Ph.D., also of the Huntsman Cancer
Institute and associate professor of oncological
sciences at the University of Utah School of
Medicine.
