Ancient signaling pathways detect, decode, and use environmental stimuli to coordinate metabolism, growth, and maturation. The power of environmental cues to trigger alterations in life history patterns has long been recognized by field biologists, and the benefit of such plasticity is clear. Variable environmental conditions demand that individuals use external information to make calculated decisions, such as whether to wait out the bad times or commit to reproduction, to maximize reproductive fitness. Indeed, evidence from work in the nematode worm, Caenorhabditis elegans, and from our work in the fruit fly, Drosophila melanogaster, has shown that sensory control of aging is evolutionarily conserved. Ablation of specific sensory neurons in the worm affects lifespan, as do mutations in genes required for sensory signal transduction. Work in our laboratory has shown that exposure to food-based odorants reduces lifespan and partially rescues the benefits of dietary restriction. Moreover, mutation of a single odorant receptor, which leaves flies broadly anosmic, results in striking longevity: up to 60% (nearly 30 days) increase in median lifespan compared to wild-type animals. While mutant flies have normal size and metabolic rate, they are resistant to starvation and hyperoxia, and they exhibit increased triglyceride storage. We seek to elucidate (i) specific olfactory stimuli that regulate longevity;(ii) which cells, molecules, and pathways transduce relevant sensory information;and (iii) how this information directs subsequent outcomes that alter lifespan. We will determine whether the increased lifespan of olfactory mutant flies relies on known longevity pathways or involves novel pathways;whether olfactory signaling acts acutely in the adult stage;and whether specific odorant receptors regulate longevity in Drosophila. Our studies will provide molecular evidence for subsequent analysis of specific molecules and biological processes that regulate aging in Drosophila. These studies may also illuminate sensory signaling networks in mammals that control development, metabolism, and aging.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
Project #
Application #
Study Section
Cellular Mechanisms in Aging and Development Study Section (CMAD)
Program Officer
Finkelstein, David B
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Michigan Ann Arbor
Schools of Medicine
Ann Arbor
United States
Zip Code
Shell, Brandon C; Schmitt, Rebecca E; Lee, Kristen M et al. (2018) Measurement of solid food intake in Drosophila via consumption-excretion of a dye tracer. Sci Rep 8:11536
Lee, Jung-Eun; Rayyan, Morsi; Liao, Allison et al. (2017) Acute Dietary Restriction Acts via TOR, PP2A, and Myc Signaling to Boost Innate Immunity in Drosophila. Cell Rep 20:479-490
Gendron, Christi M; Pletcher, Scott D (2017) MicroRNAs mir-184 and let-7 alter Drosophila metabolism and longevity. Aging Cell 16:1434-1438
Chung, Brian Y; Ro, Jennifer; Hutter, Sabine A et al. (2017) Drosophila Neuropeptide F Signaling Independently Regulates Feeding and Sleep-Wake Behavior. Cell Rep 19:2441-2450
Hoffman, Jessica M; Lyu, Yang; Pletcher, Scott D et al. (2017) Proteomics and metabolomics in ageing research: from biomarkers to systems biology. Essays Biochem 61:379-388
Harvanek, Zachary M; Lyu, Yang; Gendron, Christi M et al. (2017) Perceptive costs of reproduction drive ageing and physiology in male Drosophila. Nat Ecol Evol 1:152
Ro, Jennifer; Pak, Gloria; Malec, Paige A et al. (2016) Serotonin signaling mediates protein valuation and aging. Elife 5:
Xie, Zhongyu; Zhang, Di; Chung, Dongjun et al. (2016) Metabolic Regulation of Gene Expression by Histone Lysine ?-Hydroxybutyrylation. Mol Cell 62:194-206
Harvanek, Zachary M; Mourão, Márcio A; Schnell, Santiago et al. (2016) A computational approach to studying ageing at the individual level. Proc Biol Sci 283:
Waterson, Michael J; Chan, Tammy P; Pletcher, Scott D (2015) Adaptive Physiological Response to Perceived Scarcity as a Mechanism of Sensory Modulation of Life Span. J Gerontol A Biol Sci Med Sci 70:1088-91

Showing the most recent 10 out of 28 publications