A comparative ecological and evolutionary investigation of the genetic mechanisms of lifespan extension by caloric restriction.

Severely limiting food intake, also known as caloric restriction (CR), is one of the most reliable means of extending lifespan in a variety animals, yet the evolutionary origins and genetic mechanisms behind the response to CR are poorly understood. As part of the Mark Welch laboratory’s work to develop monogonont rotifers—microscopic, aquatic invertebrate animals—as a new model system for the study of the biology of aging, I am exploring the degree of conservation in the CR response between different reproductive types and between strains of the same species isolated from different environments.

To examine the variability in lifespan extension by CR within a species, I tested the effects of chronic caloric restriction (CCR) at multiple food levels, and of intermittent fasting (IF; feeding every-other-day) in twelve isolates representing five closely related species. Interestingly, isolates that were longest-lived under food-replete conditions were least likely to have a significant increase in lifespan under CCR, and were more likely to have a significantly shortened lifespan under IF. Short-lived strains, on the other hand, had the greatest longevity benefits from CCR and IF. While CCR generally increased both lifespan and total reproduction, IF caused increased, unchanged, or decreased lifespan, depending upon the isolate, and uniformly decreased the number of offspring. The variability in longevity and CR response suggested that lifespan is a rapidly evolving trait shaped by differences in food dynamics and predation pressure among the isolates’ native habitats. Differences in reproduction under CCR and IF, even when lifespan extension was similar, suggested that varied CR regimens extended lifespan through diverse genetic mechanisms. Over the next year we plan to examine differential gene expression between isolates that respond differently to food limitation to identify novel genetic mechanisms of lifespan extension under CR.

Figure Legend:
Survival curves for two species of Brachionus rotifers, showing the percent of animals surviving over time at each food concentration (indicated by the different colors), illustrate the variability in CR response between closely related species. The * in the legend denotes statistically significant difference in survival compared with that at 100% food levels. B. plicatilis (CGAL6) had its highest mean lifespan under 25% food conditions and died very quickly when fed every-other-day (IF). For B. manjavacas (RUS), the more that food decreased, the more that lifespan increased; the greatest mean lifespan was reached under IF conditions.