Marc Tatar, Ph. D.
Brown University

Neuroendocrine Regulation of Aging in Drosophila.

Senescence is the result of deteriorated somatic function that leads to age-dependent increase of mortality rate. Senescence is not an evolutionary adaptation, but its rate of progress can be subject to adaptive selection, as must be the case given ubiquitous species variation for longevity. Remarkably, the potential rate of senescence can also vary a great deal within the experience of a single individual. Single gene mutations in C. elegans reveal a network of genes associated with dauer formation that also can extend longevity. My research focuses on the homologous genetic and ecological system as expressed in Drosophila melanogaster.

The Drosophila life history presents potentially flexible rates of senescence during reproductive diapause. Reproductive diapause is a fly's way of overwintering - a time out to avoid bad conditions much as worms use dauer. We have found that flies senesce at slow rates during reproductive diapause. In many insects, reproductive diapause is regulated by the suppression of Juvenile Hormone (JH), and this is the case for Drosophila. We have found that JH also affects the rate of senescence during diapause, and this fact provides a clue as to how individual organisms can vary rates of aging. The process may be regulated through integrative hormones.

The homologue of worm daf-2 in flies is the insulin-like receptor, InR. We have used mutants of InR to explore the molecular homology of aging between worms and flies. Some mutants of InR can extend longevity by 80%. Along the way we have discovered that InR may affect rates of fly aging because mutants in this signal cascade are deficient in the synthesis of JH, and perhaps of ecdysone. Thus, the class of mutants that extend longevity in both worms and flies may do so because they affect the natural flexibility of senescence which is part of invertebrate life cycles.

My research program aims to understand the relationship between the insulin pathway, endocrine signals and senescence. Because the insulin pathway affects many developmental traits (such as growth rate and size), to understand how it alters senescence we need to isolate the adult components. One strategy is to use genetic methods of Drosophila to produce endocrine deficient - but normal juvenile - adults. This work will make use of tissue specific drivers to ablate adult endocrine function, and then study the consequences upon aging. A new way to see how such upstream manipulations affect somatic function and aging make use of gene statement microarrays. We are working to develop microarray chips for combinatorial experiments manipulating diapause, JH, and insulin-receptor genotypes.

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