New Scholar Award in Aging
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
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.