The dynamic interplay between an animal's perceptual system and its physiological homeostasis plays an important role in biological aging. Genetic disruption of sensory input pathways or nutrient signaling components can induce potent effects on organismal fitness and lifespan. Likewise, dietary restriction paradigms, whether through reduction of food intake or nutrient availability, enhance longevity in nearly all species sufficiently examined. Since integrative processing of sensory inputs and nutrient levels is primarily mediated by the central nervous system (CNS), the brain has emerged as an attractive frontier for understanding the contribution of environmental inputs to the biological basis of aging. However, it remains unclear how the CNS coordinates these inputs with physiological systems to control longevity and healthspan. The primary objective of this proposal is to identify and characterize central brain circuits and neural signaling substrates tha control the progression of aging using the fruit fly Drosophila melanogaster as a genetically- tractable model organism. In our first aim, we will explore how manipulation of neuropeptide F and adipokinetic hormone signaling networks influences metabolism and aging phenotypes under various dietary regimes. In our second aim, we will determine how chemosensory receptors communicate with higher-ordered processing centers to regulate fly longevity and healthspan. In our third aim, we will identify and examine novel neural signaling substrates and central brain regions critical for the progression of healthy aging in flies. Given the high degree of conservation in both the biological basis of aging and the functional architecture of the CNS across taxa, we believe these ambitious studies will provide valuable insight into how specific neuronal circuits and signaling molecules integrate environmental inputs to directly affect aging in invertebrate models, mammals, and humans.

Public Health Relevance

While modulation of sensory inputs and receptor function produces profound effects on organismal aging, the neural circuits and substrates underlying this phenomenon remain largely unknown. Elucidation of the downstream neural mechanisms important for healthy aging will provide potential therapeutic strategies that will offset prematur age-related decline.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AG042253-02
Application #
8450604
Study Section
Special Emphasis Panel (ZRG1-F05-P (20))
Program Officer
Wise, Bradley C
Project Start
2012-06-01
Project End
2014-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
2
Fiscal Year
2013
Total Cost
$52,190
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Physiology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Waterson, Michael J; Chung, Brian Y; Harvanek, Zachary M et al. (2014) Water sensor ppk28 modulates Drosophila lifespan and physiology through AKH signaling. Proc Natl Acad Sci U S A 111:8137-42
Gendron, Christi M; Kuo, Tsung-Han; Harvanek, Zachary M et al. (2014) Drosophila life span and physiology are modulated by sexual perception and reward. Science 343:544-8