Drosophila Feeding Behavior and Demographic Mechanisms of Lifespan Extension

Author: Carvalho, Gil Bastos de

Year: 2010

Degree: Dissertation (Ph.D.)

Advisors: Anderson, David J.; Benzer, Seymour

Committee Members: Anderson, David J.; Deshaies, Raymond Joseph; Sternberg, Paul W.; Baltimore, David L.

Option: Biology

DOI: 10.7907/NMN1-N566

Abstract

Why do we age? Most organisms undergo senescence, a process involving progressive functional decline culminating in death, yet this widespread phenomenon remains largely mysterious. A number of genetic and environmental factors affect longevity, the best conserved and most widely studied of which is dietary restriction (DR), a reduction of nutrient intake short of malnutrition. Since nutrient ingestion determines lifespan, any factor affecting longevity—particular food components, genetic pathways or drugs—may do so indirectly, by altering feeding behavior. This is particularly true in Drosophila, which is normally kept in conditions where food is present in excess. Moreover, since DR is applied by aging flies on two different food concentrations—diluted media are associated with an extended lifespan—animals may alter their intake in response to the change in nutrient content. Since the medium is also the only water source, this compensatory feeding would result in changes in hydration, introducing a second experimental variable. Despite these issues, Drosophila feeding behavior has classically been ignored or superficially characterized in the context of aging research, partly due to the absence of appropriate methodology. We developed two complementary assays allowing long-term measurement of food intake. Using these techniques, we present the first characterization of real-time Drosophila feeding behavior. Our results reveal gender-specific feeding trends and show that mating stimulates female appetite via the seminal Sex Peptide. Additionally, we show that ingestion is dramatically affected by food dilution or dietary additives. Animals fed concentrated media restrict their intake and are chronically thirsty. We have found that lifespan extension by classical DR paradigms is abolished in the presence of ad libitum water, challenging the long-held assumption that DR affects longevity by altering nutrient intake. We characterize a new regime that robustly prolongs lifespan irrespective of water availability, and thus likely represents a more relevant model for mammalian DR. In contrast to previous claims, demographic analysis using this paradigm indicates that DR acts not by reducing the immediate risk of death, but by slowing the accumulation of age-related damage. Our findings directly challenge current views on the mechanistic basis of DR and have broad implications for the study of aging and nutrition in model organisms.

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