Social interactions drive organism non-autonomous regulation of lifespan through pheromone perception. Christi Gendron¹, Tsung-Han Kuo², Zachary Harvanek¹, Ingrid Hansen², Scott Pletcher^1,2. 1) Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI; 2) Molecular and Human Genetics, Baylor College of Medicine, Houston, TX.

   Work from our laboratory has clearly demonstrated that sensory perception of important ecological cues is sufficient to alter Drosophila physiology and aging. To exemplify, we have shown that odorants from live yeast can limit the longevity-extending benefits of dietary restriction. We have also demonstrated that the perception of CO₂ limits fly lifespan. However, the neuronal mechanisms underlying these effects are currently unknown. To identify additional sensory functions that impact aging and to better understand the mechanisms through which they operate, we asked whether the perception of pheromones can significantly modulate health and lifespan in the fly. To avoid the confounding effects of mating, we used genetic tools to replace the cuticular pheromones of individual animals with those expressed by the opposite sex. We discovered that exposure of male flies to female pheromones, without mating, results in a significant decrease in lifespan, fat storage, and stress resistance. The effect of pheromones is robust across several laboratory and wild-caught strains, and is completely reversed following pheromone removal. To identify the sensory receptors responsible for the observed effects, we performed a candidate screen of known taste and odorant receptors. We identified a known pheromone receptor as well as a select group of receptor neurons that are required for the phenotypes described above. Furthermore, we are beginning to map the neural circuits involved. This is the first report demonstrating that the perception of pheromones from the opposite sex is sufficient to alter physiology and lifespan. Our work also defines a framework for the study of organism non-autonomous effects (i.e., the ability of a genotype of one individual to modulate the lifespan of another), and it paves the way for a mechanistic investigation of the effects of social interactions on health and longevity.