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Biomarkers of longevity: prolonged calorie restriction causes a reversal

Reducing calories over six months resulted in a decrease in fasting insulin levels and body temperature, two biomarkers of longevity.

Prolonged calorie restriction increases life span in rodents and other shorter-lived species. Whether this occurs in humans is unknown.
One theory concerning the antiaging effects of calorie restriction is its impact on metabolism, including alterations in insulin sensitivity and signaling, neuroendocrine function, stress response, or a combination of these.

Leonie K. Heilbronn, of Louisiana State University, Baton Rouge, and colleagues conducted a study to determine the effects of prolonged calorie restriction, with or without exercise, in overweight men and women.

The randomized trial, conducted between March 2002 and August 2004, included 48 healthy, sedentary men and women.
Participants were randomized to 1 of 4 groups for 6 months: control ( weight maintenance diet ); calorie restriction ( 25 percent calorie restriction of baseline energy requirements ); calorie restriction with exercise ( 12.5 percent calorie restriction plus 12.5 percent increase in energy expenditure by structured exercise ); very low-calorie diet ( 890 kcal/d until 15 percent weight reduction, followed by a weight maintenance diet ).

After six months, the control group had experienced an average weight loss of 1.0 percent; the calorie restriction group, 10.4 percent; calorie restriction with exercise, 10.0 percent; and very low-calorie diet, 13.9 percent.
Fasting insulin levels were significantly reduced at month 6 in all intervention groups.
There were no significant changes in fasting glucose or dehydroepiandrosterone sulfate ( DHEAS ) levels in any group.
Participants randomized to calorie restriction and calorie restriction with exercise had reduced average core body temperature at 6 months.
There was no change in core body temperature in the control or very low-calorie diet groups.
A technique to measure DNA fragmentation indicated reductions of DNA damage from baseline in all intervention groups.

After adjustment for changes in body composition, sedentary 24-hour energy expenditure was unchanged in controls, but decreased in the calorie restriction, calorie restriction with exercise, and very low-calorie diet groups. These metabolic adaptations were statistically different from controls.

" Our results indicate that prolonged calorie restriction caused:

1 ) a reversal in 2 of 3 previously reported biomarkers of longevity ( fasting insulin level and core body temperature );

2 ) a metabolic adaptation ( decrease in energy expenditure larger than expected on the basis of loss of metabolic mass ) associated with lower thyroid hormone concentrations; and

3 ) a reduction in DNA fragmentation, reflecting less DNA damage," the authors write.

"… longer-term studies are required to determine if these effects are sustained and whether they have an effect on human aging," the researchers conclude.

In an accompanying editorial, Luigi Fontana, of the Washington University School of Medicine, St. Louis, comments on the findings of Heilbronn et al.

" The most important contributions from this study for enhancing current understanding of the effects of calorie restriction on aging relate to the calorie restriction–mediated reductions in core body temperature, serum T3 levels, and oxidative damage to DNA, as reflected by a reduction in DNA fragmentation. The oxidative stress hypothesis of aging is currently one of the most accepted explanations for how aging occurs at the biochemical and cellular level," Fontana writes. " The study by Heilbronn et al is the first to report a significant decline in DNA damage in response to calorie restriction in humans."

" Although is it not likely that many individuals would adopt a calorie-restricted diet, the value of these studies is that they suggest possible mechanisms of aging in humans and suggest points of intervention to modify the effects of aging. Further elucidating the mechanisms that control longevity will be a major step in understanding the age dependency of a range of chronic human diseases and will help to improve the quality of life in old age."

Source: Journal of American Medical Association, 2006