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Poster Full Abstracts - Physiology and Aging
Poster board number is above title. The first author is the presenter
324
719B
Establishing a caloric restriction paradigm in
Drosophila
.
Sany Hoxha, Sarah Rollins, William Ja. Metabolism & Aging, The Scripps Research Institute,
Jupiter, FL.
Caloric restriction (CR), the reduction of nutrient intake short of malnutrition, extends the lifespan of various organisms and can improve measures of
human health. Whether mechanisms of lifespan extension are conserved between humans and model organisms is unknown. In mammals, implementing CR
is easily achieved by providing a restricted group with a fraction of the food consumed by an “ad libitum” fed group, which has unlimited food access. Due
to the difficulty in directly controlling
Drosophila
food intake, caloric restriction, performed similarly to the mammalian paradigm, has never been tested in
flies. Here, we demonstrate a system that allows measurement of food intake throughout life. Flies are housed individually in chambers that permit another
cohort of flies to be provided with a limited and measurable amount of food. This system will be used to measure fly lifespan under caloric restriction
analogous to current mammalian studies. Our work will help tease apart the differences between the various caloric and dietary restriction paradigms in
Drosophila
, strengthening our understanding of how fly models relate to mammalian systems.
720C
The effect of resveratrol and diet on lifespan and nutrient storage in Drosophila.
Michael J Polen
1
, Nikolai J Kolba
2
, Andrew Montgomery
3
, Neha
Sirohi
3
, Timothy Rudolph
2
, Hemlata Mistry
2,3
, Justin R DiAngelo
4
, Alexis Nagengast
1,2
. 1) Dept Chemistry; 2) Dept Biochemistry; 3) Dept Biology,
Widener University, Chester, PA; 4) Dept Biology, Hofstra University, Hempstead, NY.
Caloric restriction is a conserved mechanism that extends lifespan in a variety of organisms from mice to flies. Humans with a calorie restricted diet
demonstrate decreased abdominal fat storage and experience health benefits such as protection against cardiovascular disease and cancer. However, the
mechanism underlying lifespan extension in caloric restricted individuals remains unclear. The polyphenol resveratrol is naturally found in high levels in
grape skins and studies have shown that dietary exposure mimics caloric restriction and extends lifespan. To better understand the link between lifespan and
nutrient storage, we exposed a genetically homogenous strain of Drosophila to a high carbohydrate diet or 100 or 350μM resveratrol in a standard cornmeal-
molasses-yeast food source and compared their lifespan to flies raised on 0μM resveratrol in the standard food. Male flies raised on 350μM resveratrol and
the high carbohydrate diet showed an extension in lifespan. To determine if nutrient storage correlates with lifespan extension, we aged these flies for 7, 21
and 42 days and examined triglyceride levels. Flies exposed to 100μM and 350μM resveratrol exhibit decreased triglyceride levels similar to those raised on
the high carbohydrate food in the longest lived male flies. This may suggest some mechanism other than caloric restriction plays a role in lifespan extension.
One potential explanation for the lifespan phenotype is resistance to age-related oxidative damage. We are testing this by exposing the aging flies to paraquat
to induce reactive oxygen species. Future directions also include identifying the site of resveratrol accumulation in the fly to better understand the affected
target metabolic tissue.
721A
Steroid control of the mid-oogenesis checkpoint in Drosophila.
Martina Galikova, Peter Klepsatel, Thomas Flatt, Chantal Dauphin-Villemant. Institute of
Population Genetics, Vienna, Austria.
The mid-oogenesis checkpoint at stage 8/9 is tightly regulated by nutrition via ecdysteroid (20E/EcR) signaling. Under normal conditions baseline 20E
levels allow egg chambers to pass the checkpoint and to develop to stage 10, whereas under starvation programmed cell death (PCD) of mid-oogenic
chambers is triggered. To gain further insights into the steroid regulation of mid-oogenesis we genetically up- and downregulated 20E/EcR signaling in adult
females. Overexpression of the biosynthetic enzyme shadow was sufficient to increase both ovarian 20E levels and PCD at stage 8/9, thus mimicking the
effects of starvation. By contrast, when we decreased 20E by ubiquitous overexpression of the catabolic enzyme Cyp18a1 and RNAi against the biosynthetic
enzyme phantom, we observed accumulation of early vitellogenic chambers that failed to develop beyond stage 9. These defective chambers were not
cleared away via PCD typical of mid-oogenesis, since follicle cells failed to increase in size and to phagocytose nurse cell remnants. Remarkably, when
either up- or downregulating 20E/EcR signaling, nurse cells of the most distal chambers exhibited apoptotic changes. This suggests that 20E/EcR signaling
is dispensable for apoptosis of nurse cells but is required for initiating phagocytosis of nurse cells remnants in follicle cells. We next examined which cells
are responsible for the arrest at stage 9 by decreasing 20E/EcR signaling in somatic ovarian cells via EcR-RNAi, thus leaving signaling in nurse cells
unaffected. In contrast to ubiquitous impairment of 20E/EcR, EcR silencing in follicle cells did not affect 20E titers, with egg chambers proceeding to stage
10. Thus, 20E/EcR signaling appears to be required in nurse cells, but not in follicle cells, for egg chambers to pass the checkpoint. Together, our data
suggest that under normal conditions nurse cells require physiological 20E levels to pass to stage 10, whereas under starvation conditions 20E/EcR signaling
is required in follicle cells for clearing nurse cell remnants and completion of the PCD program.
722B
Localized Tissue Damage Disrupts Ecdysteroid Biosynthesis and Developmental Progression in Drosophila.
Jennifer Hackney, Omid Zolali-Meybodi,
Peter Cherbas. Department of Biology, Indiana University, Bloomington, IN.
In insects injury to specific tissues can result in a global developmental delay (e.g. prolonged larval/pupal stages) often associated with decreased levels of
ecdysone - a steroid hormone required for developmental transitions in insects. I use Drosophila as a model to examine the pathway by which tissue injury
disrupts developmental progression. Here I present data that demonstrate that imaginal disc damage inflicted early in larval development triggers
developmental delays while the effects are reduced or eliminated in older larvae. I examine the relationship between the switch in injury response (e.g.
delay/no delay) and the mid-3rd instar transition - a developmental time-point that is associated with a small pulse of ecdysone and marks the initial steps of
metamorphosis. Finally, I show that developmental delays triggered by tissue damage are associated with decreased expression of Halloween genes which
encode enzymes required for ecdysteroid biosynthesis.
723C
The Nuclear Receptor dHNF4 Regulates Carbohydrate Metabolism During Metamorphosis and Adulthood in
Drosophila
.
William E. Barry, Jason
M. Tennessen, Carl S. Thummel. Department of Human Genetics, University of Utah, Salt Lake City, UT.
Little is known about how energy homeostasis is maintained during Drosophila development, despite the significant changes in nutrient availability and