The Role of the Transcription Factor Foxo3 in Hearing Maintenance: Informed Speculation on a New Player in the Cochlea

Molecular genetics has proven to be a powerful approach for understanding early-onset hearing loss. Recent work in late-onset hearing loss uses mouse genetics to identify molecular mechanisms that promote the maintenance of hearing. One such gene, Foxo3, is ontologically involved in preserving mitochondrial function. Significant evidence exists to support the idea that mitochondrial dysfunction is correlated with and can be causal for hearing loss. Foxo3 is also ontologically implicated in driving the circadian cycle, which has recently been shown to influence the molecular response to noise damage. In this review, the molecular framework connecting these cellular processes is discussed in relation to the cellular pathologies observed in human specimens of late-onset hearing loss. In bringing these observations together, the possibility arises that distinct molecular mechanisms work in multiple cell types to preserve hearing. This diversity offers great opportunities to understand and manipulate genetic processes for therapeutic gain.