It has been recognized for nearly a century that diet modulates aging. Despite early experiments suggesting that reduced caloric intake augmented lifespan, accumulating evidence indicates that other characteristics of the diet may be equally or more influential in modulating aging. We demonstrate that behavior, metabolism, and lifespan in Drosophila are affected by whether flies are provided a choice of different nutrients or a single, complete medium, largely independent of the amount of nutrients that are consumed. Meal choice elicits a rapid metabolic reprogramming that indicates a potentiation of TCA cycle and amino acid metabolism, which requires serotonin 2A receptor. Knockdown of glutamate dehydrogenase, a key TCA pathway component, abrogates the effect of dietary choice on lifespan. Our results reveal a mechanism of aging that applies in natural conditions, including our own, in which organisms continuously perceive and evaluate nutrient availability to promote fitness and well-being.
Keywords: D. melanogaster; TCA cycle; aging; genetics; genomics; metabolism; nutrient choice; serotonin.
The foods we eat can affect our lifespan, but it is also possible that thinking about food may have effects on our health. Choosing what to eat is one of the main ways we think about food, and most animals, including the fruit fly Drosophila melanogaster, choose their foods. The effects of these choices can affect health via a chemical in the brain called serotonin. This chemical interacts with proteins called serotonin 2A receptors in the brain, which then likely primes the body to process nutrients. To understand how serotonin affected the lifespan and health of fruit flies, Lyu et al. compared flies that were offered a single food to those that could choose between several foods. The flies that had a choice of foods lived shorter lives and produced more serotonin, but these effects were reversed when Lyu et al. limited the amount of a protein called glutamate dehydrogenase, which helps cells process nutrients. These results suggest that choosing what we eat can impact lifespan, ageing and health. Human and fly brains share many similarities, but human brain chemistry is more complex, as is our experience of food. This work demonstrates that food choices can affect lifespan. More research into this phenomenon may shed further light onto how our thoughts and decision-making impact our health.
© 2021, Lyu et al.