The scent of longevity: chemosensory regulation of autophagy

Our senses do far more than help us navigate the world they may actually control how we age. Recent research has revealed that sensory inputs like smell, taste, and vision can dramatically influence our physiology and lifespan. The evidence is striking: older adults who lose their sense of smell face three times the risk of death compared to those with normal olfactory function. Similarly, mice deprived of their sense of smell remain lean even on high- calorie diets, while the mere aroma of food can negate the life-extending benefits of calorie restriction in fruit flies. Despite these remarkable discoveries, the molecular mechanisms linking our senses to aging remain insufficiently understood. One promising pathway is autophagy a cellular "cleaning" process that removes damaged components and is essential for healthy aging. While autophagy is known to be crucial for the benefits of calorie restriction and other anti-aging interventions, whether and how our sensory perceptions can regulate this vital process throughout the body has never been systematically investigated. This project aims at bridging this knowledge gap. Using the fruit fly Drosophila melanogaster as our model system, we will map exactly how sensory perception particularly the smell and taste of food influences autophagy across different tissues and nutritional conditions. By identifying the specific neural circuits that translate sensory information into cellular responses, we aim to uncover fundamental principles of how perception shapes our biology. Understanding these mechanisms could inform our approach to age-related diseases and nutritional interventions.