Calories May Not Count in Life Extension

An overwhelming amount of new data has built up over the past several decades suggesting that limiting food intake can extend almost any organism’s life, from the lowly flatworm to the ubiquitous lab mouse. Although scientists haven’t yet nailed down the mechanism behind this phenomenon, most hypotheses have focused on the number of calories in a diet—the fewer an organism takes in while still meeting its nutritional needs, the longer it’s likely to live (SN: 5/11/02, p. 291: Dogged Dieting: Low-cal canines enjoy longer life).

This idea is so prevalent that it’s frequently referred to simply as “caloric restriction.” But new research suggests that this title may be a misnomer for what actually produces longevity. A team of researchers has shown in fruit flies that shifting a diet’s relative amounts of nutrients, such as carbohydrates, protein, and fat, while only modestly cutting calories, extends life span just as much as a drastic calorie cut does.

Linda Partridge, an evolutionary geneticist at University College London, says that she and her colleagues got the idea to change the diet of their lab’s fruit flies after noticing that female flies eating a lot of yeast tended to lay more eggs than did those eating less yeast. Previous research suggested that egg laying directly correlates with life span, with more eggs leading to a shorter life.

Fruit flies in the lab normally eat a nutritious mix of sugar and yeast meant to mimic their natural diet of rotting fruit and the yeast fermenting it. “We wondered what the effects of changing the relative amounts of sugar and yeast in the food would be,” says Partridge.

Partridge’s team started by measuring the amount of time a fruit fly spent each day with its proboscis, the tube that sucks in food, extended into its chow. This information gave the scientists an idea of how much the flies typically ate.

The researchers then altered the proportions of yeast and sugar mixed together to make the flies’ food. Normally, researchers who perform caloric-restriction experiments on fruit flies make sure the insects eat less by diluting their normal chow with water. The flies spend just as much time eating but end up taking in fewer nutrients in the watery food. Rather than simply watering down the food, Partridge and her colleagues just reduced one of the diet’s two components.

While keeping the amount of sugar the same as in a normal diet, the scientists reduced the amount of yeast to less than half of what the flies normally receive. The team created a second diet using the opposite proportions, with a steady amount of yeast but less than half the normal amount of sugar. Since yeast and sugar have about the same amount of calories by weight, both of the new diets had an equal number of calories regardless of their different yeast-to-sugar ratios.

After putting groups of flies on the new diets, the scientists observed how much food the flies took in. They also kept track of how long the flies in both groups lived.

Partridge’s team made a surprising finding. Although flies eating the new diets took in about as much food as a group eating regular chow did, those on the reduced-protein diet lived about 24 days longer than the average fruit fly’s life span of 40 days. That extension, of about 60 percent, rivals the added life span of flies on a typical caloric-restriction diet.

Those flies eating less sugar also showed a modest increase in life span, although it was a markedly less-impressive extension of about 2 days.

“What this shows is that it’s not just the number of calories [that’s important for extending life]. It matters what the source of those calories is,” says Partridge. Her team published its findings in the July PLoS Biology.

Partridge says that she and her colleagues don’t yet have an idea why the yeast-restricted diets work so well at extending life span. However, she notes that the various components of yeast, made mostly of protein and lipids, may play an important role in determining longevity.

“This is a very fascinating hypothesis that we have to explore more deeply,” says Luigi Fontana, a clinical investigator at Washington University in St. Louis and at the Italian National Institute of Health in Rome. He notes that if the same concept works in people, the currently popular “low carb” diets, in which people eat large amounts of protein but fewer sugars, could be undermining the dieters’ longevity. “It’s certainly a possibility,” he says.

However, Edward J. Masoro, an emeritus professor of physiology at the University of Texas in San Antonio and a longtime researcher of caloric restriction, comments that there’s no telling whether lowering protein intake will work to lengthen life in people. Extending experimental findings from one species to another “is always fraught with difficulty,” he says.

Masoro adds that although eating fewer calories has shown some health benefits in people, scientists aren’t yet sure whether simple caloric restriction has any life-extending effects in humans. The National Institutes of Health is now running three concurrent studies of caloric restriction in nonhuman primate species, such as rhesus monkeys, that will give the best clues on whether the strategy might work in people.