SENSORY PERCEPTION & CENTRAL CONTROL OF AGING

Our laboratory established that aging and diet-restriction are regulated by olfaction and food-derived odors; that specific sensory inputs, including the smell of CO2 and the taste of water, affect fly lifespan through defined sets of neurons; that pheromonal cues activate characteristic sensory neurons and work together with reward-mediating neurons to rapidly and reversibly modulate aging; and that downstream cellular processes in peripheral tissues, including glucagon-like signaling and transsulfuration, promote survival. These advances highlight a sustained effort, facilitated by technological innovation, that has defined an area in aging biology that focuses on the acute dynamics of the response to environmental inputs and that seeks to identify neurosensory circuits and endocrine mechanisms that orchestrate changes throughout the organism to direct health and aging. In total, these findings indicate that olfaction affects adult physiology and aging in Drosophila, possibly through the perceived availability of nutritional resources, and (in combination with published work in C. elegans) that neurosensory modulation of life span is potent and evolutionarily conserved. Indeed, recent work has implicated a role for sensory receptors in mammalian longevity. In addition, this type of research is likely to have an impact beyond the molecular biology of aging. For example, our results illustrate how the genotype of one individual may affect aging in another—a phenomenon we term organism non-autonomous modulation of aging—and thereby suggest the first explicit molecular mechanism through which social interactions may influence aging and disease dynamics in nature and in human societies.

1. Libert, S., J. Zwiener, X. Chu, W. VanVoorhies, G. Roman, S. D. Pletcher. 2007. Regulation of Drosophila lifespan by olfaction and food-derived odors. Science. 315: 1133-1137 (Highlighted in Nature, Science, Developmental Cell, and many scientific and general interest news outlets) (pubmed)

2. Poon, P., Kuo, T.-H., Linford, N.J., Roman, G., and Pletcher, S.D. 2010. Carbon dioxide sensing modulates physiology and lifespan in Drosophila. PLoS Biology. 8(4): e1000356. (pubmed)

3. Gendron CM, Kuo TH, Harvanek ZM, Chung BY, Yew JY, Dierick HA, and S. D. Pletcher (2014) Drosophila lifespan and physiology are modulated by sexual perception and reward. Science. 343:544-48 (Highlighted in Nature, Science, Cell, and many scientific and general interest news outlets). (pubmed)

4. Ostojic I, Boll W, Waterson MJ, Chan TP, Chandra R, Pletcher SD, Alcedo J. 2014. Positive and Negative Gustatory Inputs Affect Drosophila Lifespan Partly in Parallel to dFOXO. Proc Natl Acad Sci USA. 111:8143-8148. (pubmed)

5. Waterson MJ, Chung BY, Harvanek ZM, Ostojic I, Alcedo J, Pletcher S.D. 2014. The Water Sensor ppk28 Modulates Drosophila Lifespan and Physiology Through AKH Signaling. Proc Natl Acad Sci USA. 111:8137-8142 (Highlighted on National public radio and similar news outlets). (pubmed)

6. Linford, N. J., J. Ro, S. D. Pletcher. 2015. Gustatory and metabolic perception of nutrient stress in Drosophila. Proc Natl Acad Sci USA. 112:2587-2592. (pubmed)