Why do hair cells and spiral ganglion neurons in the cochlea die during aging?

Age-related decline of cochlear function is mainly due to the loss of hair cells and spiral ganglion neurons (SGNs). Recent findings clearly indicate that survival of these two cell types during aging depends on genetic and environmental interactions, and this relationship is seen at the systemic, tissue, cellular, and molecular levels. At cellular and molecular levels, age-related loss of hair cells and SGNs can occur independently, suggesting distinct mechanisms for the death of each during aging. This mechanistic independence is also observed in the loss of medial olivocochlear efferent innervation and outer hair cells during aging, pointing to a universal independent cellular mechanism for age-related neuronal death in the peripheral auditory system. While several molecular signaling pathways are implicated in the age-related loss of hair cells and SGNs, studies with the ability to locally modify gene expression in these cell types are needed to address whether these signaling pathways have direct effects on hair cells and SGNs during aging. Finally, the issue of whether age-related loss of these cells occurs via typical apoptotic pathways requires further examination. As new studies in the field of aging reshape the framework for exploring these underpinnings, understanding of the loss of hair cells and SGNs associated with age and the interventions that can treat and prevent these changes will result in dramatic benefits for an aging population.