CRON reduces T3 thyroid hormone, tumor necrosis factor

June 2, 2006

summary:

Researchers examined 28 members of the Calorie Restriction Society who

had been eating a CR diet for an average of six years.

They found that CRON lowers concentrations of T3 thyroid hormone, and

also that CR decreases tumor necrosis factor alpha (TNF).

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link and full text:

http://www.eurekalert.org/pub_releases/2006-05/wuso-cra053106.php

Public release date: 31-May-2006

Contact: Jim Dryden

jdryden@...

314-286-0110

Washington University School of Medicine

Calorie restriction appears better than exercise at slowing primary aging

Investigators at Washington University School of Medicine in St. Louis

have found that eating a low-calorie yet nutritionally balanced diet

lowers concentrations of a thyroid hormone called triiodothyronine

(T3), which controls the body's energy balance and cellular metabolism.

The researchers also found that calorie restriction (CR) decreases the

circulating concentration of a powerful inflammatory molecule called

tumor necrosis factor alpha (TNF). They say the combination of lower

T3 levels and reduced inflammation may slow the aging process by

reducing the body's metabolic rate as well as oxidative damage to

cells and tissues.

Previous research on mice and rats has shown that both calorie

restriction and endurance exercise protect them against many chronic

diseases including obesity, diabetes, cardiovascular disease and some

types of cancer. However, the research has shown that only CR

increases the animals' maximum lifespan by up to 50 percent. These

animal studies suggest that leanness is a key factor in the prevention

of age-associated disease, but reducing caloric intake is needed to

slow down aging.

For the new study, researchers examined 28 members of the Calorie

Restriction Society who had been eating a CR diet for an average of

six years. Although the CR group consumed fewer calories -- averaging

only about 1,800 per day -- they consumed at least 100 percent of the

recommended daily amounts of protein and micronutrients. A second

group of 28 study subjects was sedentary, and they ate a standard

Western diet. A third group in the study ate a standard Western diet

-- approximately 2,700 calories per day -- but also did endurance

training. The researchers found reduced T3 levels -- similar to those

seen in animals whose rate of aging is reduced by CR -- only in the

people on CR diets.

But their serum concentrations of two other hormones -- thyroxin (T4)

and thyroid stimulating hormone (TSH) -- were normal, indicating that

those on CR were not suffering from the thyroid disease of clinical

hypothyroidism. The findings are published online in the Journal of

Clinical Endocrinology and Metabolism.

Interestingly, body fat levels did not affect serum T3 concentrations.

The people in the CR group and the endurance athletes had similar

amounts and composition of body fat. But although the CR group had

lower T3 levels, the exercise group had T3 levels closer to those seen

in the sedentary people who ate a standard Western diet.

" The difference in T3 levels between the CR group and the exercise

group is exciting because it suggests that CR has some specific

anti-aging effects that are due to lower energy intake, rather than to

leanness, " says first author Luigi Fontana, M.D., Ph.D., assistant

professor of medicine at Washington University in St. Louis and an

investigator at the Istituto Superiore di Sanita, Rome, Italy. " These

findings suggest that although exercise helps prevent problems that

can cut life short -- such as obesity, diabetes and cardiovascular

disease -- only CR appears also to have an impact on primary aging. "

Primary aging determines maximal length of life. Secondary aging, on

the other hand, refers to diseases that can keep a person or an animal

from reaching that expected lifespan. Eliminating factors related to

secondary aging allows more people to reach their projected length of

life. By slowing primary aging, CR may increase maximal lifespan.

In a related study in 1997, co-investigator O. Holloszy, M.D.,

professor of medicine at Washington University School of Medicine,

reported in the Journal of Applied Physiology that in rats, CR

extended life longer than exercise.

" Sedentary rats who ate a standard diet had the shortest average

life-spans, " Holloszy says. " Those who exercised by running on a wheel

lived longer, but animals on calorie restriction lived even longer. "

Earlier this year, Fontana's group reported that CR seemed to prevent

or delay primary aging in the heart. Ultrasound examinations showed

that the hearts of people on calorie restriction were more elastic

than those of age- and gender-matched control subjects. Their hearts

were able to relax between beats in a way similar to the hearts of

younger people.

This latest study targeted another marker of primary aging. The

thyroid gland produces critical hormones that play an indispensable

role in cell growth and development as well as in lipid and

carbohydrate metabolism. T4 is the main product secreted by the cells

of the thyroid gland, but most actions of thyroid hormone are

initiated by T3. Fontana says T3 controls body temperature, cellular

metabolism and to some extent, it also appears to be involved with

production of free radicals, unstable molecules that can damage cells.

All are important aspects of aging and longevity. In fact, a 2002

study in Science magazine from researchers at the National Institute

on Aging observed that men with lower body temperatures tended to live

longer those with higher body temperatures.

Fontana says lower levels of T3, cholesterol and the inflammatory

molecules TNF and C-reactive protein, combined with evidence of

" younger " hearts in people on calorie restriction, suggest that humans

on CR have the same adaptive responses as did animals whose rates of

aging were slowed by CR.

Holloszy and Fontana are getting ready to launch a 2-year study to

look at the effects of calorie restriction. Later this year, they will

begin recruiting volunteers between the ages of 25 and 45 who are

willing to go on a CR diet for 24 months.

Called the Comprehensive Assessment of the Long Term effects of

Reducing Intake of Energy (CALERIE) study, the goal is to get some

clues about whether putting a normal weight person on calorie

restriction will lower their levels of inflammation and their serum

concentrations of T3, improve their heart function and change other

markers of aging, as Fontana and Holloszy have observed in members of

the Calorie Restriction Society.

" We want to learn whether calorie restriction can reverse some of

these markers of aging in healthy people, " Holloszy says. " It's going

to be many years before we know whether calorie restriction really

lengthens life, but if we can demonstrate that it changes these

markers of aging, such as oxidative damage and inflammation, we'll

have a pretty good idea that it's influencing aging in the same way

that CR slows aging in experimental animals. "

###

Fontana L, Keline S, Holloszy JO, Premachandra BN. Effect of long-term

calorie restriction with adequate protein and micronutrients on

thyroid hormones. Journal of Clinical Endocrinology and Metabolism,

first published ahead of print May 23, 2006 as doi: 10.1210/jc 2006-0328.

This research was supported by was supported by the National

Institutes of Health.

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