Exposure to a reduced-nutrient diet without malnutrition, or dietary restriction (DR), is known to delay the onset and progression of physiological and behavioral decline over time. Dietary protein has been implicated as a key macronutrient that mediates life-extension by DR. Interestingly, research done in an invertebrate model, Drosophila melanogaster, has revealed that exposure to the smell of a major protein source, dietary yeast in the case of Drosophila, is sufficient to limit the benefits of DR on lifespan. This study evoked an exciting possibility that sensory perception of dietary protein plays a role in the modulation of aging. However, knowledge about how sensory information is processed or how it initiates widespread changes in physiology, including aging, remains rudimentary. The major objectives of this proposal are to establish neurosensory mechanisms of dietary protein perception and to evaluate its role in life-extension by DR. Our preliminary data, together with recently published results, suggested that serotonin, an important neurotransmitter, may be a key player in distinguishing protein in a food. To elucidate the specific mechanisms underlying how dietary proteins are perceived and how the relevant sensory signals are represented in the central nervous system (CNS), we will undertake careful dissection of serotonin signaling pathways using powerful genetic and neuroscience tools available in Drosophila research. We will then advance our knowledge in how sensory perception of dietary protein orchestrates global physiological changes by uncovering neuroendocrine cells that mediate dietary protein-evoked serotonin signaling. Comprehensive knowledge we gathered from these experiments will put us in a uniquely strong position to test a functional link between perception of dietary protein and diet-mediated longevity extension through serotonin signaling. The findings from our proposed studies will bring new insights into basic biology and clinical geriatric research. First, establishing connectivity between the functio of the CNS and diet-dependent longevity in fruit flies will provide a basic framework to examine similar mechanisms in more complex organisms. Second, understanding how nutrient signals are perceived and how this information is processed will foster clinical research to target neurological regulation of nutrient intake or age-associated disease progression.

Public Health Relevance

Diet composition influences the aging process of organisms across taxa. Most notably, dietary protein plays a critical role in modulating longevity. The proposed work aims to identify how organisms recognize dietary protein and how this perception can alter lifespan and associated health risks.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31AG047696-02
Application #
8889495
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Fridell, Yih-Woei
Project Start
2014-07-01
Project End
2016-03-31
Budget Start
2015-07-01
Budget End
2016-03-31
Support Year
2
Fiscal Year
2015
Total Cost
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
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Ro, Jennifer; Pak, Gloria; Malec, Paige A et al. (2016) Serotonin signaling mediates protein valuation and aging. Elife 5:
Wong, Jenny-Marie T; Malec, Paige A; Mabrouk, Omar S et al. (2016) Benzoyl chloride derivatization with liquid chromatography-mass spectrometry for targeted metabolomics of neurochemicals in biological samples. J Chromatogr A 1446:78-90
Linford, Nancy J; Ro, Jennifer; Chung, Brian Y et al. (2015) Gustatory and metabolic perception of nutrient stress in Drosophila. Proc Natl Acad Sci U S A 112:2587-92
Ro, Jennifer; Harvanek, Zachary M; Pletcher, Scott D (2014) FLIC: high-throughput, continuous analysis of feeding behaviors in Drosophila. PLoS One 9:e101107
Tan, Minjia; Peng, Chao; Anderson, Kristin A et al. (2014) Lysine glutarylation is a protein posttranslational modification regulated by SIRT5. Cell Metab 19:605-17