Amino acid recipe could be right for long life

In fruit flies, a low-calorie diet with extra amounts of methionine extends lifespan without harming fertility

Long life may stem from a proper imbalance of dietary nutrients.

A new study in fruit flies suggests that the life-extending properties of caloric restriction may be due not only to fewer calories in the diet, but also to just the right mix of protein building blocks, called amino acids. The study, published online December 2 in Nature, may help explain some of the health benefits of restricted-calorie diets.

Coupled with other data, the new study should prompt researchers to reevaluate whether it is calorie count or the nutrient composition of a diet that is most important for regulating lifespan and health, comments Luigi Fontana of Washington University in St. Louis.

Caloric restriction — a diet that contains a minimal amount of calories while maintaining healthy levels of nutrients — has been proven to extend lifespan in fruit flies, worms, mice, dogs, baboons and other organisms. Nutritious, low-cal diets also improve health in people, but scientists don’t yet know whether such diets can extend maximal lifespan in humans.

There is a downside to living longer, though. Many animals on low-calorie diets shut down their reproductive systems. Female fruit flies, for example, don’t lay eggs when fed the calorie-restricted diets. The effect makes sense, says study coauthor Matthew Piper of University College London in England.

“In times of low food, you turn off reproduction because it’s not likely that your offspring would survive. When food comes back, you turn it on again,” he says.
To test the notion that the trade-off between long life and reproduction is due to limited nutritional resources, Piper and his colleagues placed some female fruit flies on calorie-restricted diets and compared their reproductive capabilities with females on full-calorie diets. The females on low-cal diets didn’t lay as many eggs as did females on standard diets.

Next the researchers added vitamins, minerals and other nutrients to the low-cal diets to see whether nutritional deficiencies were responsible for the reduced fertility. Adding vitamins and minerals had no effect on fertility. But the addition of essential amino acids to the diet restored egg-laying capacity. Unfortunately, it also reduced lifespan in the flies.

But adding just the essential amino acid methionine restored egg-laying without reducing lifespan, the team found.

Previously, other researchers had found that reducing methionine in a normal diet could extend lifespan.

“There’s a sort of asymmetry in the relationship” between methionine levels and calorie counts, Piper says. “When food is low, lots of methionine is OK. When food is high, reducing methionine can lengthen lifespan.”

But other researchers who study aging and calorie restriction aren’t so sure that balancing amino acids will have the same effect in humans and other mammals.

“There’s always a question in my mind about the extent to which nutritional manipulation in model organisms carry over to mammals,” says Richard Weindruch, a gerontologist at the University of Wisconsin School of Medicine and Public Health in Madison. Weindruch and others have accumulated data from a variety of organisms that suggest it really is calorie content that matters for lengthening lifespan, he says.

But experiments such as this new study are contradicting that dogma, Fontana says. He has found that cutting protein content in people’s diets could reduce levels of IGF-1, a molecule involved in aging (SN: 10/25/08, p. 17).

“The idea that only calories are important is basically falling apart,” Fontana says.

Piper and his colleagues don’t know what the correct amino acid balance might be for humans, and he says it would be a nearly impossible feat to adjust people’s diets to get just the right mix. Instead, the team is investigating how tweaking amino acid content in the diet affects cells. If the researchers can identify pathways affected by amino acid imbalances, they might be able to design drugs or other therapies that could give the benefits of caloric restriction without cutting calories.

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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