Many studies on flies, mice, and more recently monkeys, have suggested that the key to a longer life is to restrict calorie intake, but a new study by US researchers suggests that the old maxim “feed a cold and starve a fever” may have some value, in that they found when it comes to coping with infection, fasting may be risky.
The new study is the work of Dr David Schneider, associate professor of microbiology and immunology at Stanford University School of Medicine and then graduate student Janelle Ayres, who has since attained her PhD and is now doing post-doctoral research at the University of California- Berkeley. They are publishing a paper about their findings this week in the journal PLoS Biology.
Many of the studies that have concluded consuming a calorie-restricted diet extends lifespan have been done under sterile lab conditions and therefore don’t properly reflect reality where we are bombarded every day by a vast array of pathogens, some of which seize hold and cause infection.
So Schneider and Ayres decided to investigate this further by measuring the appetites of infected and uninfected fruit flies: in both cases some flies had been reared on a calorie restricted diet while others had not.
Curiously, fruit flies are useful models for studying human reactions to pathogens since much of their immune response parallels ours.
They found that living on a reduced calorie diet altered the flies’ response to infection, but in ways that depended on what the flies were infected with: the response was different to different pathogens.
Ayres had already done some work on mutant fruit flies that died faster or more slowly than normal flies after being infected with pathogenic bacteria. She said she had to do so many injections on tiny flies that she couldn’t use her hand properly for a while afterwards.
One batch of mutant flies turned out to have a faulty taste receptor that caused them to eat less than other variants. So the researchers decided to use these in the new study. Also, to make sure that the effects were due to calorie restriction and not because of the mutation, they also used normal flies that were fed a calorie restricted diet for some time before being infected. The results were the same for both types of fly.
They used three different types of bacteria to infect the flies, all of which cause death in humans: Enterococcus faecalis, Salmonella typhimurium and Listeria monocytogenes. They then compared the responses of the calorie-restricted flies (including the mutants) to normally fed flies that had also been infected with these bacteria.
In the case of Enterococcus faecalis, the flies that had been on calorie restriction before infection (including the mutant flies) ate no less after infection than uninfected flies, and they survived as long as normal eaters.
In the case of the other two bacteria, the flies that had been on calorie restriction (including the mutant flies) ate less after they were infected compared with uninfected flies, but their survival patterns were different compared to normal flies, depending on which bacteria they were infected with.
The low-cal flies infected with S. typhimurium outlived likewise infected normal eaters: they survived about 15 days after infection compared with 8 days for the normal eaters.
But the low-cal flies infected with L. monocytogenes died faster than likewise infected normal eaters: they lived only 4 days, while the normal eaters lived 6 or 7.
The researchers are still trying to work out what the underlying biological reason might be for these different responses to different types of bacterial infection. But taken as a whole, the results so far suggest that the idea that a calorie-restricted diet is a good regime for life should be viewed with a little skepticism.
Schneider said:
“There’s evidence that caloric restriction seems to rev up various individual components of the immune system.”
“But in the few studies where diet-restricted animals actually have been infected experimentally, they fared poorly,” he added.
Scheider and Ayres concluded that:
“The work reported here should raise a cautionary flag, as it demonstrates that diet restriction can have complex effects on the realized immune response of a diet-restricted animal.”
The research was sponsored by the National Institutes of Health, the National Science Foundation, and the Ellison Medical Foundation.
Source: Stanford University Medical Center.
Written by: Catharine Paddock, PhD