June 01, 2005
Surprising Calorie Restriction Life Extension Result With Flies

Calorie restriction is not necessary to extend the lives of drosophila melanogaster fruit flies.

In April, the United States Centers for Disease Control and Prevention released a study challenging the conventional wisdom that eating less promotes longevity. The study found that the very thin run roughly the same risk of early death as the overweight. And now the tide seems to be turning against a common explanation for the long-standing observation that restricting food in lab organisms from yeast to mice prolongs life.

Many studies have indicated that it’s calorie reduction, rather than the specific source of calories, that increases longevity. That this effect occurs in such diverse organisms suggests a common mechanism may be at work, though none has been definitively characterized. And while calorie restriction enhances longevity in mice, it has not always done so in rats. In a new study, William Mair, Matthew Piper, and Linda Partridge show that flies can live longer without reducing calories but by eating proportionally less yeast, supporting the notion that calorie-restriction-induced longevity may not be as universal as once thought.

Dietary restriction in Drosophila involves diluting the nutrients in the fly’s standard lab diet of yeast and sugar to a level known to maximize life span. Since both yeast (which contributes protein and fat) and sugar (carbohydrates) provide the same calories per gram, the authors could adjust nutrient composition without affecting the calorie count, allowing them to separate the effects of calories and nutrients. The standard restricted diet had equivalent amounts of yeast and sugar (65 grams each) and an estimated caloric content of 521, while the yeast-restricted (65 g yeast/150 g sugar) and sugar-restricted (65 g sugar/150 g yeast) diets each had just over 860 calories. The control diet for the flies had equivalent amounts of sugar and yeast (150 grams), amounting to an estimated 1,203 calories.

First, the authors had to make sure the flies didn’t change their eating behavior to make up for a less nutritious diet. (They didn’t.) Reducing both nutrients increased the flies’ life spans, but yeast had a much greater effect: reducing yeast from control to dietary restriction levels increased median life span by over 60%.

But why this result?

Why might different factors promote longevity in flies and rats? It could be that the caloric-restriction/longevity paradigm needs more rigorous review—though a vast body of literature does support it. Or it may be that the animals use the same strategy for dealing with food shortages—shifting resources from reproduction to survival, for example—but have evolved different mechanisms for doing so that reflect each species’s life history, diet, and environment. Whatever explains the disparity, this study should give researchers interested in caloric restriction plenty to chew on.

Does this result upset the general rule that calorie restriction extends life expectancy? Perhaps Drosophila evolved in environments where calorie restriction always occurred at the same time that protein or fat restriction occurred. Natural selection might have selected for a detection of shortage of a single nutrient (or perhaps combination of nutrients) as a proxy for general calorie shortage. So perhaps the metabolism of Drosophila shfits gear when a shortage of protein or fat (or even some other nutrient found in yeast) occurs. Experiments using other food sources are needed to ascertain exactly what nutrient shortage (or nutrient ratio?) shifts Drosophila's metabolism into a state that slows aging.

Few people have the discipline to follow a calorie restriction diet for decades. Even if calorie restriction extends human lifespan (and that is as yet unproven) at best it will slow aging. Perhaps calorie restriction mimetic drugs will eventually provide a way to get the benefits (assuming there are any) of calorie without living with continuous hunger. However, development of treatments to reverse aging would provide more certain benefits and far greater benefits than the best case results for calorie restriction..

See the full research paper Calories Do Not Explain Extension of Life Span by Dietary Restriction in Drosophila.

Share |      Randall Parker, 2005 June 01 11:32 AM  Aging Diet Studies

Robert Bradbury said at June 2, 2005 7:39 AM:

There has always been some evidence that certain
types of protein restriction may extend lifespan
via mechanisms other than strict caloric restriction.
One has to look at what caloric restriction probably
does -- it probably decreases the production of
free radicals from the mitochondria and therefore
the downstream oxidative damage. However what protein
restriction does is signal the upregulation of the
recycling of proteins, esp. damaged proteins. So
you can lower the ratio of damaged proteins to good
proteins by either reducing the source of the damage
or increasing the rate at which the damage is removed.
Now, if some of the damaged proteins happen to be those
in the mitochondria (which is likely to be the case) then
protein restriction may increase the fraction of
mitochondria with undamaged proteins which are less
likely to cause free radical damage (damaged [sloppy]
mitochondrial proteins increase free radical production).

Now precisely how specific species handle protein
reduction vs. calorie reduction is an open question
as it depends in large part upon the biosynthetic
capabilities of each species with respect to the
essential amino acids for that species. This points
out one of the problems one has when making
generalizations across species.


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