Michael Cooper on Calorie Restriction in Flies

Michael Cooper wrote to me to point out his research that suggests calorie restriction (CR) does not in fact work to extend life span in houseflies:

It is widely believed that CR extends life in all species. But, it does not. My work in Musca domestica (houseflies) reveals that CR does not extend their lifespan.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15319362

In fact this work raises questions about the claims in other species as well. For example: in drosophila [fruit flies], they claim significant effects of CR, but no one has been able to directly measure the food the flies consume, the amounts are simply too small. So instead, drosophila researchers use food dilution as a mimic for CR. I believe this tactic is used in other smaller species as well.

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FASEB J. 2004 Oct;18(13):1591-3. Epub 2004 Aug 19.
Effect of caloric restriction on life span of the housefly, Musca domestica.

Cooper TM, Mockett RJ, Sohal BH, Sohal RS, Orr WC.

Department of Biological Sciences, Southern Methodist University, Dallas, Texas 75275, USA.

Caloric restriction (CR) has been found to extend the life spans of a wide variety of species, transcending phylogenetic boundaries. The objective of this study was to test the generality of this phenomenon, using the male housefly as an insect model in which food intake can be quantified precisely. Sucrose was found to promote a longer life span than diets additionally containing proteins and lipids. Flies were fed sucrose or a more complex diet ad libitum (AL), or in amounts ranging from 50% to 100% of the average amount consumed by young flies. CR shortened rather than prolonged the life span of houseflies, particularly flies fed sucrose only. The rate of oxygen consumption was not affected by caloric restriction or by the exclusion of proteins and lipids from the diet, and the reproductive activity of male flies remained unchanged by sucrose feeding. Thus, it is unlikely that the life-shortening effects of CR can be explained either in terms of an adaptive response in metabolic rate or use of a suboptimal food source. Results of this study contradict the widely held view that CR has a life-extending effect in all species.
PMID: 15319362 [PubMed - in process]

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In the discussion section of this paper, the problem of inability to directly measure food intake in small species is addressed.

Reason, I work with both drosophila and houseflies. My major efforts are actually with drosophila. I do genetic engineering, molecular biology, with drosophila, trying to understand the aging process. So, I am intimately familiar with the care and feeding of this species.

In mice CR, the food is directly measured. As far as I know, all mammal studies have used direct measurement of food. It is in the small species that direct measurement becomes impractical. Houseflies may be close to the practical limit for direct measurement.

There are other more complicated ways of determining food intake, such as; radioactive or other means of labeling. So far as I know, these labeling methods have not been used in CR studies.

The plot thickens. There are certainly a number of studies indicating that fruit flies do experience the benefits of CR - but doubts raised over experimental methods would mean that a more rigorous examination of those findings is called for. On the other hand, if it were the case that fruit flies benefit from CR while houseflies do not ... well, that would seem to be a difference worth investigating more closely. Pinning down the biochemical and genetic roots of CR will have long term benefits for our health and longevity - hence all this careful work with flies.