Evidence for Serotonin Signaling to be Important in Calorie Restriction

Calorie restriction produces improved health and extended longevity in most species, with a much larger effect in short-lived species that tend to have very plastic life spans in response to circumstances. One of the many interesting results to emerge from calorie restriction research is that this effect on health and longevity can be manipulated by altering systems of perception, work that has largely been carried out in flies and nematodes. Calorie restriction effects can be reduced by exposing flies to the presence of more food without letting them eat it, for example, and tinkering with the sensory neurons responsible for identifying and characterizing food content can induce some of the effects of calorie restriction without reducing calorie intake. Researchers here link serotonin signaling with the mechanisms of food sensing, and show that disrupting it has a fairly sizable effect on fly life span under some dietary conditions:

Limiting the amount of protein eaten, while still eating enough to avoid starving, has an unexpected effect: it can slow down aging and extend the lifespan in many animals from flies to mice. Previous work suggests that how an animal perceives food can also influence how fast the animal ages. For example, both flies and worms actually have shorter lifespans if their food intake is reduced when they can still "smell" food in their environment. However, the sensory cues that trigger changes in lifespan and the molecular mechanisms behind these effects are largely unknown.

Researchers therefore asked whether fruit flies recognize protein in their food, and if so, whether such a recognition system would influence how the flies age. Flies that had been deprived of food for a brief period tended to eat more protein than other flies that had not been starved. The researchers then revealed that serotonin, a brain chemical that can alter the activity of nerve cells, plays a key role in how fruit flies decide to feed specifically on foods that contain protein. Further experiments revealed also that flies age faster when they are allowed to interact with protein in their diet independently from other nutrients, despite eating the same amount. Disrupting any of several components involved in serotonin signaling protected the flies from this effect and led to them living almost twice as long under these conditions.

Researchers propose that the components of the recognition system work together to determine the reward associated with consuming protein by enhancing how much an animal values the protein in its food. As such, it is this protein reward or value - rather than just eating protein itself - that influences how quickly the fly ages. Further work is now needed to understand how the brain mechanisms that allow animals to perceive and evaluate food act to control lifespan and aging.

Link: http://dx.doi.org/10.7554/eLife.16843

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