Homeostatic maintenance and age-related functional decline in theDrosophilaear

The widespread loss of hearing is one of the major threats to future wellbeing in ageing human societies. Amongst its various forms, age-related hearing loss (ARHL) carries the vast bulk of the global disease burden. The causes for the terminal decline of auditory function, however, are as unknown as the mechanisms that maintain sensitive hearing before its breakdown. We here present an in-depth analysis of maintenance and ageing in the auditory system of the fruit flyDrosophila melanogaster. We show thatDrosophila, just like humans, display ARHL and that their auditory life span is homeostatically supported by a set of evolutionarily conserved transcription factors. The transcription factors Onecut (closest human orthologues: ONECUT2, ONECUT3), Optix (SIX3, SIX6), Worniu (SNAI2) and Amos (ATOH1, ATOH7, NEUROD1) emerged as key regulators acting upstream of core sensory genes, including components of the fly’s molecular machinery for auditory transduction and amplification.