The Physiological and Metabolic Basis of the Fecundity/Longevity Trade-Off in Drosophila

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In many organisms curtailed reproduction increases lifespan. Conversely, extended lifespan is often accompanied by reduced reproduction. Interestingly, decreased food intake without malnourishment (dietary restriction) also promotes lifespan while concomitantly reducing reproduction. These observations suggest that the longevity-reproduction trade-off might represent an energetic resource allocation trade-off whereby food limitation might divert resources away from reproduction and make them available for somatic maintenance and survival. However, the tradeoff in energy allocation between fecundity and metabolic storage is not quantitative exact and dietary restriction can increase lifespan in gonadectomized worms (Caenorhabditis elegans) and sterile flies (Drosophila melanogaster), findings which are at odds with the resource allocation model. In contrast to C. elegans that lack the entire gonad, worms (and flies) that lack germ cells only are long-lived and dietary restriction cannot further extend longevity in these individuals, suggesting that signals from the germline may oppose those of the somatic gonad to regulate aging. Therefore, although current knowledge indicates that nutrient metabolism, reproduction and aging represent interconnected regulatory axes, the actual mechanisms underlying the trade-off between reproduction and longevity remain largely unknown. The main goal of the research proposed here is to gain novel insights into the mechanisms underlying the reproduction-longevity trade-off, a central problem in life history evolution and in the biology of aging. Specifically, we seek to test the hypothesis that the reproductive and nutritional regulatory axes converge onto the same mechanisms that affect aging. We propose to investigate this hypothesis by using the fly model Drosophila melanogaster to examine the consequences of dietary restriction on (1) longevity in normally reproducing and sterile flies (with and without proliferating germline) and on (2) gene expression profiles in reproductive and somatic tissues.