Calorie Restriction Trial in Humans Suggests Benefits For Age-Related Disease

Science News
from research organizations
Calorie restriction trial in humans suggests

benefits for age-related disease
Date:
March 22, 2018
Source:
Cell Press
Summary:
One of the first studies to explore the effects of calorie restriction on
humans showed that cutting caloric intake by 15 percent for two years
slowed aging and metabolism and protected against age-related disease.
The study found that calorie restriction decreased systemic oxidative
stress, which has been tied to age-related neurological conditions such as
Alzheimer's and Parkinson's diseases, as well as cancer, diabetes, and
others.
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FULL STORY
This graphical abstract depicts the effects of a 2-year calorie restriction (CR)
trial in healthy, non-obese humans, which found evidence that prolonged CR
enhances resting energy efficiency, resulting in decreased oxidative damage to
tissues and organs.
Credit: Redman et al./Cell Metabolism
One of the first studies to explore the effects of calorie

restriction on humans showed that cutting caloric intake by
15% for 2 years slowed aging and metabolism and protected
against age-related disease. The study, which will appear
March 22 in the journal Cell Metabolism, found that calorie
restriction decreased systemic oxidative stress, which has
been tied to age-related neurological conditions such as
Alzheimer's and Parkinson's diseases, as well as cancer,
diabetes, and others.
"Restricting calories can slow your basal metabolism, and if by-products of

metabolism accelerate aging processes, calorie restriction sustained over
several years may help to decrease risk for chronic disease and prolong life,"
says lead author Leanne M. Redman, associate professor of Clinical Sciences at
Pennington Biomedical Research in Baton Rouge, LA.
CALERIE (Comprehensive Assessment of the Long-Term Effects of Reducing

Intake of Energy) was the first randomized controlled trial to test the metabolic
effects of calorie restriction in non-obese humans. The second phase of the
study reports results from 53 healthy, non-obese men and women between ages
21 and 50 who cut calories by 15% over 2 years and underwent additional
measurements for metabolism and oxidative stress. The calorie reductions were
calculated individually through the ratio of isotopes absorbed by the
participants' molecules and tissues over 2 weeks, a technique that accurately
pinpoints a weight-maintenance calorie level.
Those in the calorie restriction group lost an average of almost 9 kg, although
they did not follow a particular diet and weight loss was not the study's goal. No
adverse effects, such as anemia, excessive bone loss, or menstrual disorders
were noted; in fact, both trials led to improvements in mood and health-related
quality of life. "We found that even people who are already healthy and lean may
benefit from a calorie restriction regimen," Redman says.
In lab animals, calorie restriction lowers core body temperature and resting
metabolic rate. Redman emphasized that CALERIE looked at the effects of
calorie restriction on aging, not weight loss, where discussions of "fast" or
"slow" metabolism most often arise. "We know from mammalian studies that the
smaller the mammal, the faster their metabolism and the shorter their longevity,"
she says.
Many factors, such as antioxidant mechanisms and dietary and biological factors,
influence metabolism, Redman says, but current theories hold that a slower
metabolism is most beneficial for healthy aging and that organisms that burn
energy most efficiently should experience the greatest longevity.
"The CALERIE trial rejuvenates support for two of the longest-standing theories
of human aging: the slow metabolism 'rate of living' theory and the oxidative
damage theory," she says. The latter ties overproduction of free radicals to
oxidative damage to lipids, proteins, and DNA, leading to chronic diseases such
as atherosclerosis, cancer, diabetes, and rheumatoid arthritis.
While the number of participants was relatively small and the duration short in
the context of a human lifespan, biomarkers of aging were improved in study
participants. Next steps include establishing robust biomarkers of human aging
and examining the effects of calorie restriction in conjunction with antioxidant
foods or substances like resveratrol, which mimic calorie restriction.
Caloric Restriction: Key to Better

Health, Longer Life?
Written by Hilary Macht
A long-awaited study has found that limiting caloric intake not only preserves health but
also increases longevity. The paper, which was published in Nature Communications,
involved decades of study of rhesus monkeys, is said to resolve the debate over
whether caloric restriction (CR) extends lifespan. 1, 2,3
“The main message from this study is that the amount you eat influences how you age,”
said Rozalyn Anderson, study author and associate professor, Department of Medicine,
University of Wisconsin-Madison. “The work shows that in primates, reducing calorie
intake in adulthood and later in life confers benefits in terms of both health and
survival.” 1, 4
The latest findings represent the collaboration between two competing research teams
—one at the University of Wisconsin-Madison (UW) and the other at the National
Institute on Aging (NIA)—that worked together in an effort to explain their differing
observations on the impact of CR on longevity. 1, 2, 3
Both teams had initially set out to study the effects of caloric restriction--defined as a
diet comprised of about 30% fewer calories but providing the same nutrients as a
standard diet—on rhesus monkeys, who as they age are vulnerable to many of the
same diseases as humans. 1, 2, 3
In 2009, the UW research team reported significant extension of life and reductions in
cardiovascular disease, cancer and insulin resistance in the monkeys whose diets were
calorically restricted. But in 2012, while the NIA group also found better health among its
CR monkeys, the researchers observed no significant improvement in survival. 1, 2, 3
The conflicting findings cast doubt on the benefits of CR on longevity and appeared to
go against nearly a century of laboratory research showing that CR significantly extends
lifespan, albeit in non-primates. Beginning in the 1930s, for example, researchers found
that laboratory rats and mice live up to 40% longer when fed a diet that has at least 30%
fewer calories than they would normally consume. Substantial research over the last
two decades has also demonstrated the benefits of CR in short-lived organisms such as
yeast, nematodes and fruit flies. 1, 2, 3, 5
But, after sifting through all the information from the two study sites including data from
nearly 200 monkeys, the authors concluded that CR is indeed associated with longer
survival. The observed discrepancies, they said, stemmed from a variety of factors
including: diet composition (the NIA monkeys ate naturally-sourced foods while the UW
group ate relatively more processed foods with higher sugar content); the age of the
monkeys when the restricted diets were introduced (eating less confers benefits in adult
primates but not in younger animals—which, by the way, is unlike in rodents, where the
earlier the animals begin CR the longer the resulting lifespan); and genetics. 1, 2, 3
Any Benefits for Humans?
Of course, the research begs the question of what all this means for humans. The study
authors say their findings suggest that CR mechanisms are likely translatable to human
health. “The profound similarities between humans and rhesus monkey in the rate of
aging, the types of diseases of aging that occur, and how they manifest clinically makes
it extremely likely that the mechanisms of CR in monkeys will be translatable to human
health and aging too.” Anderson said. 1, 4
It appears that researchers who have looked at CR in humans agree. “There are
numerous examples from well-studied human cohorts that there is a likely benefit for
reduced-calorie diets to promote healthy aging and lifespan extension in humans,” said
Leanne Redman, Ph.D, associate professor and investigator in the CALERIE study at
the Pennington Biomedical Research Center at Louisiana State University in Baton
Rouge. “As humans strive for the fountain of youth in today's obesogenic environment,
looking to dietary and nutritional approaches for improved health across the lifespan is
the most obvious choice.” 6, 7
Indeed, one theory is that CR evolved as a protective response to enable animals—and
humans—to survive periods of food shortage. But this evolutionary advantage might
seem to backfire in today’s environment of overabundant and chronic accessibility to
food combined with a trend of reduced physical activity. 6
Others see in the latest research the value of diet composition. “The more wholesome
and less-refined diet consumed by the NIA monkeys—which contained substantially
less sucrose, more favorable lipid and protein sources and higher fiber relative to the
Wisconsin diet—appears to have benefits independent of the level of CR,” said Susan
B. Racette, Ph.D., professor at Washington University School of Medicine in St. Louis.
“This finding is encouraging for human application, given the challenges of adhering to a
calorically-restricted diet long-term.” 8, 9

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Science News

from research organizations

Calorie restriction trial in humans suggests

Credit: Redman et al./Cell Metabolism

One of the first studies to explore the effects of calorie

"Restricting calories can slow your basal metabolism, and if by-products of

CALERIE (Comprehensive Assessment of the Long-Term Effects of Reducing

Caloric Restriction: Key to Better

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