Scientists are a cautious lot, and funding is available for careful studies that replace sound assumptions with even more sound established facts. Now that calorie restriction (or dietary restriction, DR) research is attracting so much funding at the development end of R&D, you'll see more studies aimed at firming up the foundations. Take this open access paper for example:

One of the promising advances towards the goal of uncovering the mechanisms by which DR extends life was the discovery that the effect is evolutionarily conserved. However, even with the use of short-lived model organisms for relatively rapid lifespan experiments, the mechanisms remain elusive. This is likely to be largely due to the complexity of physiology involved in determining length of life, but may be also in part due to technical issues in experimental design hampering a clear path of progress.

The ease with which complexity can be introduced into these studies can be illustrated by the large effects on fly lifespan caused by very small changes in nutrition. For example, substituting one source of the dietary yeast Saccharomyces cerevisiae, with another from a different supplier in an otherwise identical diet can have large effects on fly lifespan. Similarly, lifespan differences have been reported due to the use of different bacterial strains as food for Caenorhabditis elegans or by interchanging casein and soy peptone as the source of dietary protein for rodents. In fact, a recent article has proposed that DR itself may have arisen as a by-product of laboratory life as animals are unintentionally subjected to selective breeding in the presence of an artificially rich nutritional environment. Clearly, these issues need to be addressed if we are to uncover the molecular mechanisms of DR.

As might be expected from the weight of existing evidence for calorie restriction to extend healthy longevity, increasing the rigor of the experiments didn't prevent the beneficial effects:

In this study, we have examined the effect of laboratory stock maintenance, genotype differences and microbial infection on the ability of dietary restriction (DR) to extend life in the fruit fly Drosophila melanogaster. None of these factors block the DR effect.