Though caloric restriction can increase lifespan in Drosophila, a new study shows it can have complex effects on the immune system.

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BRISBANE: Dietary restrictions found to improve longevity in many species can cause unwanted changes in the immune system, researchers have found.

Restricting calorie intake in the fruit fly Drosophila melanogaster makes it more resistant to some infections, but decreases survival rates for others, according to a report today in PLoS Biology.

These complicated effects cast doubt on the idea that calorie restriction could be a cure-all treatment to improve human longevity, said co-author David Schneider, a biologist at Stanford University in California, USA.

"We [have] demonstrated that during an immune response, the fly actively alters its nutrition and… this leads to feedback loops that can aid or collapse the immune response," Schneider said.

Collapsed immune response

Losing your appetite is a common response to many infections, in both humans and animals, but why it happens isn't clear.

Although scientists once thought that this loss of appetite, called 'anorexia', was induced by pathogens to weaken the host, the response is so common that some scientists believe it may actually be a helpful part of the host's immune reaction.

Scientists know that there is a link between immunity and ageing, and moderate dietary restriction increases the lifespan of many laboratory animals, leading to speculation that dietary restriction could help humans live longer too.

However, laboratory animals usually aren't exposed to a normal range of pathogens, which could hide a weakening of the immune system that counteracts the beneficial effects of dietary restriction.

Schneider and his student, Janelle Ayres, tested that idea by infecting three groups of Drosophila with a variety of pathogens.

Complex effects

One strain had a mutant gustatory receptor, which causes it to naturally eat very little, a second, normal strain was fed diluted food solution to mimic the effects of anorexia, and another normal strain was fed undiluted food.

Surprisingly, the dietary-restricted flies had better survival rates than the normal flies for some pathogens, such as Salmonella, but worse survival rates for other pathogens, such as Listeria.

Schneider and Ayres observed that dietary restriction switched off a particular kind of immune response called melanisation, but it didn't explain all of the effects of anorexia, Schneider said, so they plan to test anorexic and normal flies with microarrays, which compare the activity of a wide variety of genes.

Elizabeth McGraw, an entomologist who studies infections at the University of Queensland in Brisbane, Australia, said that the work was important because pathways that link diet and ageing are currently being targeted for pharmaceutical development.

"[The] work cautions that dietary restriction has complex effects on animals and that restriction with the goal of slowing the ageing process could have the unwanted side effect of reducing survival to infections," McGraw said.