Monkey in the Middle
Authors: Trivedi Bijal P. 
Published: August 2003

Beware, food-loving humans: Proof of calorie restriction's life-extending effects is approaching your species. A new study suggests that dieting rhesus monkeys live twice as long as normal and identifies three physiological changes shared between the primates and enduring humans.

Calorie restriction is the only treatment that consistently prolongs the lives of numerous species, from yeast to mice. Whether the regime works in humans remains unclear, in part because a study that measures any intervention's effect on human life-span would be prohibitively expensive and time-consuming (see

Walford
et al.
abstract and comments

). To circumvent that problem, scientists seek physiological parameters--or biomarkers--that provide surrogate measures of aging (see
Miller Perspective
). Such biomarkers would likely maintain youthful concentrations in long-lived creatures. In the new work, gerontologist George Roth of the National Institute on Aging (NIA) in Baltimore, Maryland, and colleagues tested whether biomarkers of calorie-restricted monkeys also characterize long-lived humans.

For 5 years, Roth's team has fed 30 rhesus monkeys 30% fewer calories than controls. Preliminary data add to previous evidence that calorie restriction works in primates: To date, 13% of the treated animals and 24% of the controls have perished. Although not statistically significant, the results suggest that calorie-restricted monkeys die at half the rate of normal animals.

Roth's team previously showed that body temperatures and insulin concentrations of the calorie-restricted monkeys hover well below normal, consistent with observations of dieting mice and rats. For their age, the monkeys also harbor large amounts of dehydroepiandrosterone sulfate (DHEAS), a steroid hormone with an uncertain role in aging whose amounts decline with age. To investigate whether these biomarkers also correlate with longevity in people, the scientists analyzed data gathered as part of the Baltimore Longitudinal Study of Aging (BLSA), the world's longest running study of human aging. Among deceased human males, those who lived longer tended to have lower body temperatures and insulin concentrations and higher DHEAS concentrations.

No one knows how calorie restriction works, but recent evidence suggests that it causes organisms to shift metabolic strategies (see
"High-Octane Endurance--Yeast in the Metabolic Fast Lane Live Longer"
). The monkeys' low body temperatures mean that their metabolism is producing less heat than normal, so "a lower body temperature is a symptom of metabolic change," says Roth. In addition, reduced insulin concentrations could curb signaling pathways that normally trigger growth at the expense of longevity, he proposes.

"This paper is a clever marriage of two NIA data sets [BLSA and rhesus] that advances the knowledge of aging in primates," says gerontologist Richard Weindruch of the University of Wisconsin, Madison. Next, says zoologist Steven Austad of the University of Idaho in Moscow, researchers will need to "determine whether these are general biomarkers or just a quirk of the data set." Numbers already available from studies similar to BLSA, but with fewer subjects, could answer the question quickly, he adds. If the results hold up, they could help scientists identify physiological changes that extend life. Gourmets shouldn't immediately renounce their Port Salut and profiteroles, but they might want to brace their bellies for the possibility.

--Bijal P. Trivedi

G. S. Roth, M. A. Lane, D. K. Ingram, J. A. Mattison, D. Elahi, J. D. Tobin, D. Muller, E. J. Metter, Biomarkers of caloric restriction may predict longevity in humans.
Science
297
, 811 (2002).
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