Diet restriction in Drosophila melanogaster. Design and analysis.

Diet restriction (DR) was first shown to extend adult survival in Drosophila only a bit longer than a dozen years ago. Limiting the amount of dietary yeast was sufficient to increase life span. In the short time since this initial observation, work with Drosophila has revealed several insights into the mechanisms of DR. It has also uncovered many unanticipated technical issues. This paper describes how resolving the way we study DR in Drosophila is a prerequisite to discover the way nutrition modulates aging. Key empirical problems include the necessity of measuring the impact of DR upon life span with multiple levels of diet, analysis of the demographic response to diet with mortality data and, in the context of reaction norms, methods of diet modification, and uncertainty as to how diet dilution translates to changes in actual nutrient uptake. We review the accumulated literature of DR in Drosophila from this methodological lens to distill four important results: yeast restriction alone is sufficient to increase survival; diet affects survival through two distinct physiological responses, starvation and longevity assurance; mortality has no memory of its past with respect to nutrition; the molecular operation of DR may involve processes of deacetylation via Sir-2 and Rpd-3. Finally, it remains unknown whether or not DR functions through insulin-related signaling.