Flies that Choose a Poor Diet Have a Shorter Lifespan than those Forced into a Poor Diet

This interesting study shows that when given the choice to consume sugar or protein, flies consume a lot of sugar and exhibit reduced life span as a result. Feeding the same proportional mix of sugar and protein to flies without giving them the choice of what to consume does not reduce life span to the same degree, however. The researchers identify specific signaling responsible for this outcome, involved in the neuronal regulation of metabolism, a part of the only partially explored feedback loop between diet and appetite. This is all fascinating, but it is hard to say whether it has any near term relevance to health in humans.

What constitutes a good diet remains a matter of continuous debate. The typical way of addressing such questions in a laboratory setting would be to compare groups given diets with different macronutrient compositions and measure their lifespans. But in real life, food is neither presented nor consumed that way. First, foods vary in their composition of macronutrients. Second, all creatures tend to have innate preferences towards certain foods. Taking these discrepancies into account, would we see a connection between macronutrients and longevity in a more naturalistic, choice-based food environment?

Researchers set out to address this topic in a widely used model system, the fruit fly Drosophila melanogaster. In the first set of experiments, one group of wild-type fruit flies spent their lives on a diet consisting of equal amounts of sugar and protein (fixed diet). The second group received the same amount and ratio of sugar and protein, but they could choose between the two foods (choice diet). Then, the amount of food consumed and lifespans were measured and compared across both groups. Alas - and perhaps unsurprisingly - flies given the choice between sugar and protein consumed far more sugar and lived less long than those given no choice in the matter.

However, the reduced longevity of the 'sweet-toothed' flies could not be attributed solely to sugar-induced toxicity. Even flies given up to three times as much sugar as protein in the fixed-diet group had an intermediate lifespan. Additionally, other measures, such as intestinal permeability and locomotion, were unaltered by the choice diet, at least in young flies. Not even a major messenger molecule in the insulin signaling pathway (dFOXO), a key culprit in diet-induced longevity, was greatly affected by a choice-driven diet. Instead, it appeared that being presented with the choice itself led to increased sugar consumption and reduced longevity.

Researchers were able to show that a serotonin receptor called 5HT2A was responsible for the choice-induced reduction in lifespan. However, when 5HT2A was removed, flies on a choice diet no longer had shortened lifespans, even though they consumed just as much sugar as the wild-type flies. Researchers suspected that variations in internal nutrients could be behind the observed changes in lifespan. They compared a large number of metabolites relevant for converting food to energy in flies raised on both diets, and with or without 5HT2A. Over 80% of these metabolites did not change. However, in flies raised on a choice-diet, four amino acids (lysine, glutamine, asparagine, and aspartate) increased in a 5HT2A-dependent manner.

Link: https://doi.org/10.7554/eLife.66755

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